Diastolic Blood Pressure
Introduction
Section titled “Introduction”Diastolic blood pressure (DBP) is the lower number in a blood pressure reading, representing the pressure in the arteries when the heart muscle relaxes between beats and refills with blood. It reflects the resistance of the blood vessels to blood flow when the heart is at rest. Blood pressure is typically measured using a standard mercury column sphygmomanometer, often after a rest period, with multiple readings frequently averaged for accuracy.[1] Studies often adjust raw DBP values for individuals taking anti-hypertensive medication to account for treatment effects.[2]DBP is one of several quantitative blood pressure traits analyzed, alongside systolic blood pressure (SBP) and pulse pressure (PP), which is the difference between SBP and DBP. While correlated with SBP, DBP measures distinct physiological features contributing to cardiovascular health.[3]
Biological Basis
Section titled “Biological Basis”Diastolic blood pressure is a complex, heritable trait influenced by numerous genetic factors.[4] Genome-wide association studies (GWAS) have been instrumental in identifying specific genetic loci associated with DBP. Significant associations have been found in a large region on chromosome 12q24 encompassing genes such as SH2B3, ATXN2, and TRAFD1, as well as TBX3/TBX5.[5] Another notable locus is PLEKHA7 on chromosome 11p15.[5] Other genes, including CCL20, WDR69, and CDH13, have also shown associations with DBP.[4] Suggestive evidence of association has also been observed for loci in or adjacent to ULK4, CSK/ULK3, and CACNB2.[5]Research also explores genes within the renin-angiotensin-aldosterone pathway due to their known roles in blood pressure regulation.[4] These studies often employ methodologies like family-based association testing (FBAT) and generalized estimating equations (GEE) to analyze additive genetic effects, with meta-analyses combining results from diverse cohorts to enhance statistical power.[4]
Clinical Relevance
Section titled “Clinical Relevance”Elevated diastolic blood pressure is a key indicator of hypertension, generally defined as DBP ≥ 90 mm Hg.[3]Hypertension is a major risk factor for a range of cardiovascular diseases, including heart attack, stroke, and kidney disease. Understanding the genetic underpinnings of DBP is crucial because it contributes to a comprehensive cardiovascular risk profile, even as it reflects partly distinct physiological processes compared to systolic blood pressure.[3]
Social Importance
Section titled “Social Importance”Hypertension, characterized by persistently high blood pressure, is a significant global health concern, affecting a large proportion of the adult population. The identification of genetic loci influencing DBP provides critical insights into the biological mechanisms that regulate blood pressure. This genetic knowledge can contribute to the development of more effective diagnostic tools, personalized prevention strategies, and targeted therapeutic interventions for hypertension, ultimately reducing the substantial public health burden and improving cardiovascular outcomes worldwide. Large-scale studies, such as the Framingham Heart Study and trans-ancestry meta-analyses, are vital for advancing this understanding across diverse populations.[4]
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Genome-wide association studies (GWAS) of diastolic blood pressure rely on extensive sample sizes to detect the subtle genetic effects associated with this complex trait.[6]Studies often exclude single nucleotide polymorphisms (SNPs) with insufficient sample sizes (e.g., less than 10,000) or those exhibiting significant heterogeneity across cohorts, which can influence the statistical power and scope of detected associations.[6] The choice of statistical models, such as additive genetic models or generalized estimating equations, can also impact the detection of various genetic effects, including recessive ones.[4], [6] The quality of genetic data, particularly imputed genotypes, is a critical factor. Rigorous quality control measures are applied, including filtering SNPs based on minor allele frequency, Hardy-Weinberg equilibrium P values, call rates, and imputation quality scores (e.g., r2 < 0.5).[1], [4], [6] While essential for data integrity, these filters can limit the spectrum of genetic variation available for analysis and potentially affect the comprehensiveness of identified associations. Furthermore, the selection of SNPs for replication stages, sometimes based on interim analyses or specific p-value thresholds (e.g., P < 10−5), may introduce selection bias or winner’s curse, even with strategies implemented to minimize such influences.[2]
Phenotypic Complexity and Variability
Section titled “Phenotypic Complexity and Variability”Diastolic blood pressure is a dynamic physiological characteristic, influenced by a multitude of interacting factors, which inherently introduces variability into its.[2] While the test-retest reliability of blood pressure measurements is generally reported between 0.65 and 0.75, detecting small genetically-determined changes (e.g., 0.5 mm Hg) at the individual clinical level remains challenging, thereby necessitating large-scale population studies to discern group-level genetic effects.[2] This intrinsic variability requires meticulous and consistent protocols across studies to ensure robust findings.
Handling of participants on antihypertensive medication and outlier values also presents methodological challenges. Different studies employ varying strategies, such as adding fixed values (e.g., 5 or 10 mm Hg) to measured diastolic blood pressure for treated individuals, or using Winsorization techniques to cap extreme values at a certain number of standard deviations.[6], [7], [8] These diverse approaches to medication adjustment and outlier management can introduce heterogeneity across studies and affect the comparability and interpretation of genetic associations.
Environmental Influences and Generalizability
Section titled “Environmental Influences and Generalizability”Environmental factors play a significant role in influencing inter-individual differences in diastolic blood pressure, including dietary sodium and potassium intake or alcohol consumption.[2] However, these crucial environmental exposures are often not comprehensively measured or adjusted for in large-scale genetic studies due to practical limitations, which can potentially reduce statistical power or mask underlying genetic effects.[2] Although research increasingly investigates gene-environment interactions, the complete spectrum of these complex influences on blood pressure variation remains an active area of discovery.[8], [9], [10] The generalizability of genetic findings is also constrained by the ancestral composition of the study populations. For instance, some meta-analyses are specifically conducted within populations of particular ancestries, such as East Asians, which limits the direct applicability of their findings to other diverse populations.[6] While efforts are made to use multi-ancestry reference panels for genotype imputation, differences in genetic architecture and linkage disequilibrium patterns across diverse ancestral groups can impact the transferability and replication of genetic associations.[7] Broader representation in genetic studies is essential to enhance the global applicability of identified genetic loci.
Incomplete Genetic Architecture and Causal Inference
Section titled “Incomplete Genetic Architecture and Causal Inference”Despite substantial advancements in identifying genetic loci associated with diastolic blood pressure, its complete genetic architecture is still being elucidated, with ongoing discoveries of novel variants indicating remaining knowledge gaps.[7], [11], [12] Estimates of heritability for blood pressure traits can vary, and a significant portion of the phenotypic variance may still be unexplained by currently identified genetic variants, a phenomenon often referred to as “missing heritability”.[13] This suggests that numerous other genetic factors, potentially with smaller effects or involved in complex interactions, await discovery.
Establishing a definitive causal relationship between genetic variants, diastolic blood pressure, and subsequent health outcomes is a complex endeavor.[3] Mendelian randomization approaches, although powerful, encounter limitations in differentiating the causal effects of various blood pressure measures due to the scarcity of genetic variants specifically associated with only one blood pressure trait.[3] Furthermore, the assumption that genetic effects on outcomes are solely mediated via blood pressure, rather than through alternative biological pathways, requires careful consideration and further investigation to avoid misinterpretation of causal links.
Variants
Section titled “Variants”Genetic variations play a crucial role in influencing an individual’s predisposition to various health traits, including diastolic blood pressure. Several single nucleotide polymorphisms (SNPs) and their associated genes have been identified as contributors to blood pressure regulation, often through their involvement in metabolic pathways, cellular signaling, or cardiovascular function. Understanding these variants helps to elucidate the complex genetic architecture underlying blood pressure variability and hypertension.
Among the identified variants, rs653178 within the ATXN2gene is notably associated with diastolic blood pressure. This SNP is located in a large 1-megabase block of linkage disequilibrium on chromosome 12q24, which also encompasses other genes such asSH2B3 and TRAFD1.[5] ATXN2 (ataxin-2) encodes a protein involved in RNA processing and translation, and its dysfunction is linked to neurodegenerative disorders; however, its role in blood pressure regulation may involve broader cellular processes or interactions within this genomic region.[5] Another gene, CLCN6, which encodes a chloride channel protein, has also been identified as a nearest gene for expression quantitative trait loci (eQTLs) associated with blood pressure, suggesting its involvement in ion transport and fluid balance critical for vascular tone and overall cardiovascular health.[5] Chloride channels are fundamental to cellular excitability and electrolyte homeostasis, processes that directly impact blood pressure.
Other variants linked to metabolic and transport functions also contribute to blood pressure traits. The GCKR gene, for which rs780094 is a variant, encodes glucokinase regulator, a protein that controls the activity of glucokinase, a key enzyme in glucose metabolism. Variations inGCKRcan influence glucose and lipid levels, which are well-established risk factors for hypertension and cardiovascular disease. Similarly,SLC39A8 (Solute Carrier Family 39 Member 8), with variants like rs13107325 , rs11724128 , and rs17032400 , is involved in zinc transport, a micronutrient essential for numerous enzymatic reactions and immune function, both of which can impact vascular health and inflammation relevant to blood pressure regulation. The GALNT18 gene, represented by rs10047474 , encodes an enzyme involved in O-glycosylation, a post-translational modification crucial for protein stability and cell signaling. While its direct link to diastolic blood pressure is still being explored, alterations in protein glycosylation can affect cell-cell interactions and receptor functions within the cardiovascular system, thereby modulating blood pressure mechanisms.[4] Genome-wide association studies have consistently identified multiple loci influencing blood pressure phenotypes, highlighting the polygenic nature of this trait.[9] Further genetic regions and genes, including those without extensive detail in the immediate context, underscore the broad genetic landscape influencing blood pressure. Variants such as rs13125101 , rs16998073 , and rs12509595 are associated with the PRDM8 - FGF5 locus. FGF5 (Fibroblast Growth Factor 5) is known for its role in cellular growth and differentiation, including angiogenesis, while PRDM8 is involved in gene regulation, both potentially affecting vascular development and function. The HERPUD1 - CETP locus, with variant rs247617 , involves CETP(Cholesteryl Ester Transfer Protein), a well-studied gene in lipid metabolism and cardiovascular disease, where its activity impacts cholesterol levels, a known risk factor for hypertension.HERPUD1 is involved in cellular stress responses. Genes like ZPR1 (rs964184 ), RGL3 (rs167479 , rs2291516 , rs318719 ), and LMAN1L (rs11636952 ) represent diverse biological pathways. ZPR1 (Zinc Finger Protein 1) is involved in cell proliferation, RGL3 is a signaling molecule in the Ras pathway critical for cell growth and differentiation, and LMAN1Lplays a role in protein quality control. Variations in these genes could impact vascular smooth muscle function, endothelial integrity, or inflammatory processes, all of which contribute to the complex regulation of diastolic blood pressure.[14] These findings highlight the multifaceted genetic contributions to blood pressure regulation, spanning metabolic, signaling, and cellular maintenance pathways.[12]
Key Variants
Section titled “Key Variants”Definition and Physiological Context of Diastolic Blood Pressure
Section titled “Definition and Physiological Context of Diastolic Blood Pressure”Diastolic blood pressure (DBP) represents the minimum arterial pressure observed during the cardiac cycle, specifically when the heart rests between beats and refills with blood.[6]It is a fundamental component of overall blood pressure, alongside systolic blood pressure (SBP), which measures the peak pressure during heart contraction.[4]DBP is crucial for understanding cardiovascular health, as it reflects the resistance in the peripheral arteries and the heart’s ability to relax.[3]Its value, often expressed in millimeters of mercury (mmHg), contributes to other derived cardiovascular metrics such as mean arterial pressure (MAP), calculated as SBP/3 + 2DBP/3, and pulse pressure (PP), defined as SBP minus DBP.[6]
Approaches and Operational Definitions
Section titled “Approaches and Operational Definitions”The accurate of DBP is critical for both clinical diagnosis and research. Standardized protocols typically involve trained and certified observers using either a random zero sphygmomanometer or an automatic cuff-oscillometric device.[6] Participants usually undergo a rest period of at least 5 minutes in a sitting position before measurements are taken, often multiple times (e.g., three times or an average of two measurements per arm).[6] For individuals taking anti-hypertensive medication, DBP values are commonly adjusted in research settings by adding a constant, such as 5 mmHg, to the measured DBP to account for treatment effects.[6]In analytical contexts, DBP phenotypes are often processed as residuals derived from regression models, accounting for demographic and anthropometric variables like sex, age, age-squared, and body mass index (BMI).[4]
Classification Systems and Diagnostic Criteria for Hypertension
Section titled “Classification Systems and Diagnostic Criteria for Hypertension”DBP plays a key role in the classification and diagnosis of hypertension. Hypertension is clinically defined by specific DBP thresholds, typically when DBP is consistently ≥90 mmHg, or by a self-report of taking medication for blood pressure treatment.[2] Conversely, normotensive individuals are often characterized by a DBP ≤85 mmHg and no use of anti-hypertensive medications.[2] While DBP is a continuous trait, these cut-off values allow for a categorical classification of individuals into hypertensive or normotensive groups, which is essential for guiding clinical interventions and public health strategies.[3]Elevated DBP is a significant risk factor, positively associated with increased risk of cardiovascular events, including coronary heart disease and ischemic stroke, as well as structural changes like increased left ventricular mass and wall thickness.[3]
Clinical Assessment and Protocols
Section titled “Clinical Assessment and Protocols”Diastolic blood pressure (DBP) is an objectively measured physiological parameter, typically assessed in a clinical setting using a standard mercury column sphygmomanometer, such as a portable Baumanometer 300 Model or a wall-mounted Baumanometer E98169.[1] Consistent protocols involve participants being seated for at least five minutes before the initial.[1] DBP is specifically determined by the fifth Korotkoff sound, signifying the disappearance of arterial sounds, and the reported value is often an average of multiple readings, typically one nurse/technician reading and two physician readings, to ensure accuracy and minimize white-coat effects.[1] As a continuous variable measured in millimeters of mercury (mmHg), DBP values are often adjusted to account for confounding factors and treatment effects.[14] For individuals actively taking blood pressure-lowering medication, a standardized adjustment, commonly adding 10 mmHg (or sometimes 5 mmHg in specific studies), is applied to their raw DBP readings to estimate their untreated blood pressure levels.[3]Furthermore, research often analyzes DBP as residuals derived from regression models that statistically account for covariates such as sex, age, age-squared, and body mass index (BMI), which helps isolate genetic or other specific influences on DBP.[4] Long-term average DBP values are also utilized in studies to provide a more stable and representative measure over time.[4]
Presentation Patterns and Diagnostic Implications
Section titled “Presentation Patterns and Diagnostic Implications”Diastolic blood pressure is a critical component of overall blood pressure assessment, alongside systolic blood pressure (SBP), pulse pressure (PP), and the diagnosis of hypertension.[3]Clinically, elevated DBP is a key criterion for diagnosing hypertension, with a DBP of 100 mmHg or higher, or being on antihypertensive treatment, often defining a ‘case’ in diagnostic frameworks.[14] While DBP phenotypes are frequently analyzed independently, many genetic variations associated with DBP also show correlations with other blood pressure phenotypes, indicating shared physiological pathways.[5] Genetic studies have identified numerous loci with diagnostic significance for DBP, highlighting its complex etiology. For instance, significant association signals for DBP have been found in a large linkage disequilibrium block on chromosome 12q24, which includes genes such as SH2B3, ATXN2, and TRAFD1.[5] Other notable loci include TBX3/TBX5 on chromosome 12q24 and PLEKHA7 on chromosome 11p15.[5] Suggestive evidence for association has also been observed near ULK4, CSK/ULK3, and CACNB2.[5]Additionally, specific single nucleotide polymorphisms (SNPs) in genes likeCCL20, CDH13, and LPP have been associated with both long-term DBP and SBP, further underscoring the genetic interplay in blood pressure regulation.[4]
Factors Influencing Diastolic Blood Pressure Variability
Section titled “Factors Influencing Diastolic Blood Pressure Variability”Diastolic blood pressure exhibits significant inter-individual variation, influenced by a range of demographic, physiological, and genetic factors. Age and sex are consistently recognized as major determinants, with research models frequently incorporating these, along with BMI, as covariates to adjust DBP values.[4] Specifically for DBP, age-squared is often included in statistical models to better capture non-linear age-related changes in this pressure component.[4] Furthermore, an individual’s medication status is a crucial variable, as antihypertensive treatments directly impact DBP levels, necessitating specific adjustments to raw measurements to accurately reflect underlying physiological states.[3] The genetic landscape of DBP also contributes to its heterogeneity, with studies revealing different genetic associations across populations of varying ancestries, such as European, South Asian, and East Asian cohorts.[3] This phenotypic diversity underscores the complex genetic architecture underlying DBP and the importance of considering population-specific genetic backgrounds. Analyzing phenotypes like long-term averaged DBP, which integrates measurements over multiple examination cycles, helps to mitigate short-term fluctuations and capture a more stable representation of an individual’s typical DBP, thereby improving the power to detect subtle genetic influences and clinical correlations.[4]
Genetic Predisposition
Section titled “Genetic Predisposition”Diastolic blood pressure (DBP) is a highly heritable trait, with genetic factors playing a significant role in individual variations. Genome-wide association studies (GWAS) have identified numerous genetic loci associated with DBP, indicating its polygenic nature, where many common variants each contribute a small effect . The regulation of DBP is a complex interplay of various biological mechanisms, encompassing molecular, cellular, genetic, and systemic factors.
Physiological Regulation of Diastolic Blood Pressure
Section titled “Physiological Regulation of Diastolic Blood Pressure”The regulation of diastolic blood pressure involves intricate interactions between various organs and molecular pathways that control vascular tone and fluid balance. Key players include the kidneys, which manage salt and water excretion, and the vasculature, whose smooth muscle cells dictate arterial resistance. For instance, theKCNK3gene, encoding a potassium channel, is crucial in regulating vascular tone, with mutations in this gene being associated with pulmonary hypertension.[14] Furthermore, variations in genes that influence renal function, such as ARHGAP24 (involved in podocyte formation), OSR1 (a transcription factor affecting renal mass and function), SLC22A7 (a renal solute transporter), and TBX2 (a determinant of renal function), can significantly impact blood pressure.[14]Common genetic variation that elevates atrial natriuretic peptide levels, which interact with natriuretic peptide receptors coded byNPR1, has been shown to lower blood pressure, highlighting the role of these circulating hormones in fluid homeostasis.[15]
Genetic Architecture and Associated Molecular Mechanisms
Section titled “Genetic Architecture and Associated Molecular Mechanisms”The heritable component of blood pressure is substantial, with numerous genetic loci identified as influencing diastolic blood pressure. A significant block of genetic variation on chromosome 12q24, encompassing genes such asSH2B3, ATXN2, and TRAFD1, has shown strong association with DBP, notably at rs3184504 , rs653178 , and rs17630235 .[5] Other genes like PLEKHA7 (chromosome 11p15, rs11024074 , rs381815 ) and TBX3/TBX5 (chromosome 12q24, rs2384550 ) are also implicated.[5] At a molecular level, the DBH gene, which codes for dopamine beta hydroxylase, plays a critical role by catalyzing the conversion of dopamine to norepinephrine, thereby influencing the sympathetic nervous system and blood pressure regulation.[15] A rare allele of DBH (rs3025380 ) encoding a Gly88Ala substitution, has been linked to a considerable reduction in blood pressure.[15] Additionally, the PDE3Agene, whose pharmacological inhibitors are known to lower blood pressure, points to the involvement of cyclic nucleotide signaling pathways.[14] The IGFBP3gene, which modulates insulin-like growth factors (IGFs) that affect vascular smooth muscle cell function, further illustrates the diverse molecular pathways involved in DBP control.[14]
Epigenetic and Environmental Interactions
Section titled “Epigenetic and Environmental Interactions”Beyond direct genetic variants, epigenetic modifications and interactions with environmental factors contribute to DBP variability. The PRDM6gene acts as an epigenetic regulator, influencing the phenotypic plasticity of vascular smooth muscle cells by suppressing differentiation and maintaining their proliferative potential.[14]This suggests that epigenetic mechanisms can modulate vascular health and, consequently, blood pressure. Environmental factors, such as dietary sodium intake, alcohol consumption, and age, are known modifiers of blood pressure and can interact with genetic predispositions.[2]For example, specific gene-sodium interactions, such as atrs13211840 , have been identified as influencing diastolic blood pressure.[10] Genes like SLC16A9 have been highlighted in studies examining gene-alcohol interactions related to blood pressure.[9] Moreover, polymorphisms in the mitochondrial dynamin-like GTPase OPA1have shown age-dependent associations with blood pressure and hypertension.[13] Low levels of serum Neuregulin 4 (NRG4) are also strongly associated with elevated blood pressure.[13]
Pathophysiological Implications and Life Course Development
Section titled “Pathophysiological Implications and Life Course Development”Disruptions in the homeostatic regulation of diastolic blood pressure can lead to significant pathophysiological consequences. Hypertension, characterized by persistently high blood pressure, substantially increases the risk of vascular and cerebrovascular diseases, impacting mortality and quality of life.[9]Studies of rare Mendelian disorders have demonstrated that mutations in genes affecting renal salt handling can severely impact blood pressure, underscoring the kidney’s critical role in hypertension pathogenesis.[2]The development of blood pressure over a lifetime also holds predictive value, as variation in DBP during adolescence and early adulthood is associated with a subsequent adult risk of coronary heart disease and stroke.[12]Understanding the genetic and environmental factors that shape DBP throughout childhood and adolescence is therefore crucial for gaining insights into the life course development of adult hypertension and cardiovascular disease.[12]
Diagnostic Utility and Risk Assessment
Section titled “Diagnostic Utility and Risk Assessment”Diastolic blood pressure (DBP) serves as a fundamental metric in the diagnosis and monitoring of hypertension, a critical risk factor for cardiovascular disease. Standardized protocols for DBP assessment, including a rest period of 5 minutes, the use of bias-free instrumentation, and timed, repeat measurements by trained personnel, are essential for accurate clinical evaluation, although test-retest reliability ranges from approximately 0.65 to 0.75.[2], [16] For individuals receiving antihypertensive medication, observed DBP values are typically adjusted by adding 5 mm Hg to account for treatment effects, thereby ensuring a more accurate representation of underlying blood pressure status.[5], [10], [16]The diagnostic threshold for hypertension is commonly defined as a DBP ≥ 90 mm Hg or current pharmacological treatment for hypertension.[2], [5], [16]Beyond basic , the integration of multiple DBP readings over time to calculate a long-term average DBP, adjusted for factors such as age, sex, and body mass index (BMI), significantly enhances precision in risk assessment.[6], [17]Genetic risk scores (GRS), which incorporate multiple single nucleotide polymorphisms (SNPs) associated with DBP, such as those inPLEKHA7 (rs11024074 ), CCL20 (rs7591163 ), and rs11105364 , provide a quantitative measure of an individual’s genetic predisposition to elevated DBP and hypertension.[4], [5], [6]These GRS have demonstrated highly significant associations with both deviation from mean DBP and the odds of hypertension, with their predictive value improving as more DBP-associated SNPs are included, thus contributing to personalized risk stratification.[5], [17]
Prognostic Significance for Cardiovascular Outcomes
Section titled “Prognostic Significance for Cardiovascular Outcomes”Elevated diastolic blood pressure is a significant prognostic indicator for a range of adverse cardiovascular outcomes and structural cardiac changes. Research consistently demonstrates a graded relationship between DBP and increased cardiovascular risk, a finding that holds true despite inherent variability in blood pressure measurements.[2]Specifically, an increase of 10 mmHg in DBP is positively associated with an elevated risk of coronary heart disease (CHD), underscoring its direct link to the development and progression of atherosclerosis.[3]Furthermore, higher DBP values are strongly associated with a substantially increased risk of ischemic stroke, particularly those involving large vessels, thereby emphasizing its critical role in cerebrovascular health.[3]Beyond these macrovascular events, elevated DBP is also linked to detrimental structural remodeling of the heart, manifesting as increases in left ventricular mass and left ventricular wall thickness.[3]These robust associations highlight the paramount importance of DBP control in mitigating the long-term burden of cardiovascular morbidity and mortality.
Genetic and Environmental Factors Influencing Diastolic Blood Pressure
Section titled “Genetic and Environmental Factors Influencing Diastolic Blood Pressure”The variability in diastolic blood pressure among individuals arises from a complex interplay of genetic, demographic, and environmental factors. Genetic studies have identified numerous loci associated with DBP, including specific genes likePLEKHA7, ULK4, CSK/ULK3, CACNB2, CCL20, CDH13, and WDR69.[4], [5] While the effect of individual genetic variants on DBP may be subtle, large-scale studies are capable of detecting these influences, thereby contributing to a comprehensive understanding of blood pressure regulation and informing future personalized medicine approaches for prevention.[2]In addition to genetic predispositions, demographic factors such as age, sex, and body mass index (BMI) significantly account for observed DBP variation, with untreated DBP generally found to be higher in African Americans and males compared to other groups.[17]Environmental exposures, particularly dietary sodium and potassium intake or excessive alcohol consumption, also contribute to inter-individual differences in DBP.[2] Crucially, gene-environment interactions, such as the interaction between the UST gene (rs13211840 ) and sodium intake, have been identified as influencing DBP, suggesting potential avenues for targeted lifestyle interventions and prevention strategies tailored to an individual’s genetic profile.[10]
Pharmacogenetics of Diastolic Blood Pressure
Section titled “Pharmacogenetics of Diastolic Blood Pressure”Pharmacogenetics explores how an individual’s genetic makeup influences their response to medications, including those used to manage diastolic blood pressure (DBP). Understanding these genetic variations can help optimize drug selection and dosing, aiming for improved efficacy and reduced adverse effects. Genetic factors can impact DBP regulation through various mechanisms, from drug metabolism to the function of drug target proteins and signaling pathways.
Genetic Variants Affecting Drug Metabolism and Disposition
Section titled “Genetic Variants Affecting Drug Metabolism and Disposition”Genetic variations in drug-metabolizing enzymes significantly influence the pharmacokinetics of antihypertensive medications, thereby impacting DBP control. A notable example involves the cytochrome P450 (CYP450) enzyme family, which is crucial for the metabolism of many drugs and xenobiotics in the liver. Specifically, CYP1A2 is a widely expressed enzyme, representing a substantial portion of hepatic CYP450 enzymes, and it mediates the metabolism of numerous medications.[2] Polymorphisms within CYP1A2, such as rs762551 , have been shown to affect the metabolism of substances like caffeine and have been suggested to associate with DBP.[2]Such variations can lead to altered drug clearance rates, resulting in higher or lower drug concentrations in the body, which may necessitate dose adjustments to achieve optimal DBP reduction while minimizing side effects. Beyond specific drug metabolism, CYP450 enzymes also play a role in cellular metabolism of arachidonic acid derivatives, some of which influence renal function, peripheral vascular tone, and overall blood pressure regulation.[2]
Pharmacodynamic Effects and Drug Target Variability
Section titled “Pharmacodynamic Effects and Drug Target Variability”Variations in genes encoding drug targets or proteins within DBP-regulating signaling pathways can alter an individual’s therapeutic response to antihypertensive drugs. The renin-angiotensin-aldosterone pathway, a primary target for many DBP-lowering medications, has been investigated for genetic associations, though some studies have reported only weak associations of specific SNPs within these genes with DBP or arterial stiffness.[4] Despite weak individual SNP associations, the pathway itself remains a critical pharmacodynamic target, and variants could theoretically influence receptor binding, enzyme activity, or signaling cascades, thereby affecting drug efficacy. Other genes identified as having associations with DBP, such as SH2B3 (rs3184504 ), ATXN2 (rs653178 ), TRAFD1 (rs17630235 ), PLEKHA7 (rs11024074 ), CCL20 (rs7591163 ), and CDH13 (rs3096277 ), represent potential targets or modulators of DBP regulation.[5] While direct pharmacogenetic interactions with specific drugs for these genes are not extensively detailed, their association with DBP suggests that polymorphisms could influence the physiological response to interventions aimed at lowering blood pressure.
Clinical Implementation of Pharmacogenetic Insights
Section titled “Clinical Implementation of Pharmacogenetic Insights”The integration of pharmacogenetic information into clinical practice holds promise for personalizing DBP management. By identifying an individual’s genetic variants, particularly those affecting drug metabolism like CYP1A2, clinicians could make more informed decisions regarding drug selection and initial dosing strategies. For instance, individuals with genetic profiles indicating rapid or slow metabolism of a particular antihypertensive drug might receive adjusted doses to prevent subtherapeutic levels or reduce the risk of adverse drug reactions. While the genetic effects on DBP for common SNPs may appear small, sometimes on the order of 0.5 mm Hg, the cumulative impact of multiple variants or those with substantial effects on drug-response pathways can be clinically meaningful.[2] However, widespread clinical implementation requires robust evidence demonstrating the utility of these genetic insights in improving patient outcomes, supported by clear clinical guidelines that translate complex genetic data into actionable prescribing recommendations.
Frequently Asked Questions About Diastolic Blood Pressure
Section titled “Frequently Asked Questions About Diastolic Blood Pressure”These questions address the most important and specific aspects of diastolic blood pressure based on current genetic research.
1. My parents have high DBP. Will I likely have it too?
Section titled “1. My parents have high DBP. Will I likely have it too?”Yes, diastolic blood pressure is a heritable trait, meaning it can run in families. While many genes influence DBP, if your parents have high DBP, you may have an increased genetic predisposition. However, lifestyle factors also play a significant role in its development.
2. Can healthy habits overcome my family’s DBP risk?
Section titled “2. Can healthy habits overcome my family’s DBP risk?”Absolutely. While genetics influence your baseline risk for high DBP, it’s a complex trait, meaning lifestyle choices like healthy eating and regular exercise are crucial. These habits can help manage and potentially mitigate your genetic predisposition, improving your overall cardiovascular health.
3. Does my ethnic background change my DBP risk?
Section titled “3. Does my ethnic background change my DBP risk?”Yes, research shows that genetic risk factors for DBP can differ across various populations. Studies, including trans-ancestry meta-analyses, are important to understand these differences, for example, in Hispanic and African American populations, to develop more targeted health strategies.
4. What would a DNA test tell me about my DBP risk?
Section titled “4. What would a DNA test tell me about my DBP risk?”A DNA test could identify specific genetic variations associated with DBP, such as those near genes like SH2B3 or PLEKHA7. This information provides insight into your genetic predisposition, which can contribute to a more comprehensive understanding of your cardiovascular risk profile and guide personalized prevention.
5. Why do some people have normal DBP even with unhealthy habits?
Section titled “5. Why do some people have normal DBP even with unhealthy habits?”Diastolic blood pressure is influenced by many genetic factors, so some individuals may have a more protective genetic makeup. Even with less healthy habits, their genes might offer resilience against DBP elevation, highlighting the complex interplay between genetics and lifestyle.
6. If I take medication for DBP, do my genes still matter?
Section titled “6. If I take medication for DBP, do my genes still matter?”Yes, your genes still matter. While medication helps manage DBP, genetic factors contribute to its underlying regulation. Research often adjusts for anti-hypertensive medication effects, recognizing that the genetic basis of DBP remains relevant for understanding your long-term risk and potential treatment responses.
7. Does stress make my DBP higher if I have a genetic risk?
Section titled “7. Does stress make my DBP higher if I have a genetic risk?”Diastolic blood pressure is a dynamic characteristic influenced by many interacting factors, and stress is known to impact blood pressure. While specific gene-stress interactions for DBP are still being researched, if you have a genetic predisposition, stress could potentially exacerbate your risk, making management crucial.
8. I have normal SBP, but my DBP is often high. Why is that?
Section titled “8. I have normal SBP, but my DBP is often high. Why is that?”DBP and SBP, while correlated, measure distinct physiological features of your cardiovascular system. Your DBP reflects the resistance of blood vessels when your heart rests, and it can be elevated independently, indicating specific aspects of your heart health.
9. Can knowing my genetic DBP risk help me prevent heart issues?
Section titled “9. Can knowing my genetic DBP risk help me prevent heart issues?”Absolutely. Understanding your genetic predisposition for DBP provides critical insights into the biological mechanisms regulating your blood pressure. This knowledge can contribute to developing personalized prevention strategies and potentially more targeted interventions to reduce your overall cardiovascular risk.
10. Why do blood pressure medications work differently for people?
Section titled “10. Why do blood pressure medications work differently for people?”The effectiveness of blood pressure medications can vary due to individual genetic differences. Your unique genetic makeup, influencing various biological pathways, can affect how your body processes and responds to specific drugs, which is why personalized medicine is an area of ongoing research.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Sung, Y. J., et al. “Gene-smoking interactions identify several novel blood pressure loci in the Framingham Heart Study.” Am J Hypertens, vol. 28, no. 3, 2014, pp. 343–50.
[2] Newton-Cheh C, et al. “Genome-wide association study identifies eight loci associated with blood pressure.” Nat Genet, 2009.
[3] Surendran P, et al. “Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.”Nat Genet, 2016.
[4] Levy D, et al. “Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness.”BMC Med Genet, 2007.
[5] Levy D, et al. “Genome-wide association study of blood pressure and hypertension.”Nat Genet, 2009.
[6] Li C, et al. “Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.” Circ Cardiovasc Genet, 2017.
[7] Wain, L. V., et al. “Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.” Hypertension, 2017.
[8] Simino, J et al. “Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia.” Am J Hum Genet, vol. 95, no. 4, 2014, pp. 436-451.
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