Urate
Introduction
Section titled “Introduction”Urate, also known as uric acid, is a metabolic end product derived from the breakdown of purines, which are essential components of DNA and RNA found in various foods and produced naturally by the body. Once formed, urate circulates in the blood serum and is primarily excreted by the kidneys. Maintaining appropriate urate levels is crucial for overall health, as both excessively high or low concentrations can have physiological consequences.
Biological Basis
Section titled “Biological Basis”Urate is the final product of purine catabolism in humans. Purines, such as adenine and guanine, are metabolized through a series of enzymatic reactions, with xanthine oxidase playing a key role in the conversion of xanthine to uric acid. The balance of urate in the body is maintained by a delicate interplay between its production and its excretion, predominantly through the kidneys. Genetic factors significantly influence an individual’s urate levels. For example, theGLUT9 gene (also known as SLC2A9) has been identified as a major genetic determinant of serum uric acid levels, affecting how urate is transported and reabsorbed in the kidneys.[1]
Clinical Relevance
Section titled “Clinical Relevance”of serum urate levels is a common diagnostic tool in clinical practice. Elevated urate levels, a condition known as hyperuricemia, are defined by specific thresholds. For men, hyperuricemia is typically defined as a serum urate concentration greater than 7.5 mg/dl (450 µmol/l), while for women, it is greater than 6.2 mg/dL (372 µmol/l).[1]Hyperuricemia is a primary risk factor for gout, a painful inflammatory arthritis caused by the crystallization of uric acid in joints. Beyond gout, persistently high urate levels have been associated with an increased risk of kidney stones, chronic kidney disease, hypertension, metabolic syndrome, and cardiovascular disease. Conversely, very low urate levels (hypouricemia) can also indicate underlying health issues, though it is less common.
Methods
Section titled “Methods”Serum urate is typically measured using enzymatic-colorimetric methods.[1] For accurate results, blood samples are usually collected in the morning after participants have fasted for at least 12 hours and have been sitting for 15 minutes. Serum aliquots are then immediately obtained and stored at -80°C to preserve sample integrity.[1] The lower limit of detection for these assays is generally around 0.2 mg/dl, with a typical range of 0.2–25.0 mg/dl. The precision of these measurements is high, with intra-assay coefficients of variation often around 0.5% and inter-assay coefficients of variation around 1.7%.[1]
Social Importance
Section titled “Social Importance”The prevalence of conditions linked to abnormal urate levels, particularly hyperuricemia and gout, has significant public health implications. Gout, for instance, affects millions worldwide, leading to chronic pain, reduced quality of life, and substantial healthcare costs. Understanding the genetic and environmental factors contributing to urate levels allows for better risk assessment, preventive strategies, and personalized treatment approaches. Lifestyle modifications, such as dietary changes (e.g., reducing purine-rich foods and sugary drinks), can influence urate levels. Furthermore, research into the genetic underpinnings of urate regulation, such as the role ofGLUT9, contributes to a deeper understanding of metabolic health and may pave the way for novel therapeutic interventions to manage urate-related disorders.
Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”Studies investigating genetic associations with urate levels often face several methodological and statistical limitations that can influence the interpretation and robustness of findings. While some cohorts may involve a substantial number of individuals, the use of related individuals, as seen in the Sardinian cohort, can introduce statistical challenges if not appropriately modeled, potentially leading to inflated effect sizes or reduced effective sample sizes for independent observations.[1] Furthermore, the reliance on genotype imputation, a common practice to infer untyped genetic variants, inherently introduces a degree of uncertainty into genotype calls, which can impact the accuracy of association signals.[2] The need for replication studies, such as those conducted in specific island populations, underscores that initial findings require independent validation to confirm their generalizability and reduce the likelihood of spurious associations.[3]
Generalizability and Phenotypic Heterogeneity
Section titled “Generalizability and Phenotypic Heterogeneity”The generalizability of findings from genetic studies of urate levels can be constrained by the demographic characteristics of the cohorts examined. Many studies, including those on the Adriatic coast and in Sardinia and Chianti, focus on populations with relatively homogeneous ancestries, which may limit the direct applicability of identified genetic associations to more diverse populations, such as African Americans, where the genetic architecture of urate may differ.[3]Additionally, variations in the precise methods for urate assessment, such as the use of different enzymatic-colorimetric assays (e.g., Bayer versus Roche Diagnostics), can introduce inter-cohort variability and potential inconsistencies in the phenotype definition across studies.[1]Although efforts are made to standardize sample collection (e.g., fasting and sitting), a single time-point may not fully capture the dynamic nature of urate levels, which can fluctuate due to various physiological and environmental factors.
Unaccounted Environmental Factors and Genetic Complexity
Section titled “Unaccounted Environmental Factors and Genetic Complexity”Despite significant advances in identifying genetic contributors to urate levels, a comprehensive understanding of its etiology remains elusive due to the complex interplay of genetic and environmental factors. Environmental confounders, such as dietary habits, lifestyle choices, and medication use, are known to substantially influence urate levels, yet these factors are often difficult to fully capture, quantify, and account for in large-scale genetic association studies. The concept of “missing heritability” suggests that a significant portion of the genetic variance for urate levels may still be unexplained by identified common genetic variants, pointing towards the potential roles of rare variants, structural variations, or complex gene-gene and gene-environment interactions that current study designs may not fully elucidate. Consequently, while specific genes likeGLUT9have been associated with urate levels, the complete genetic and environmental architecture contributing to individual differences in urate remains an active area of research.[1]
Variants
Section titled “Variants”The genetic landscape influencing serum urate levels is complex, involving numerous genes that regulate the production, breakdown, and excretion of uric acid. Key among these are genes encoding transporters responsible for moving urate across cell membranes, particularly in the kidneys and intestines. Variations within these genes can significantly alter an individual’s urate levels, affecting their predisposition to conditions like hyperuricemia and gout.
One of the most significant genes involved in urate homeostasis isSLC2A9(Solute Carrier Family 2 Member 9), which encodes a high-capacity urate transporter. This protein plays a crucial role in reabsorbing urate in the kidneys, thereby regulating its concentration in the blood.[4] Variants in SLC2A9are strongly associated with serum urate levels, urate excretion, and the risk of gout.[4], [5] For instance, the variant rs11722228 in SLC2A9has shown a highly significant association with serum urate levels, underscoring its impact on maintaining proper urate balance.[6] Other SLC2A9 variants such as rs1850733 and rs3775947 also contribute to this genetic predisposition, influencing the transporter’s efficiency and subsequently affecting circulating urate concentrations.
Another critical gene is ABCG2(ATP Binding Cassette Subfamily G Member 2), which encodes a transporter protein primarily involved in urate excretion from the body, particularly in the intestines and kidneys. Reduced function of theABCG2transporter can lead to decreased urate excretion and elevated serum urate levels, increasing the risk of hyperuricemia and gout.[7], [12] The rs2231142 (Q141K) variant within ABCG2is particularly well-studied and is considered a strong candidate for causally influencing urate levels, as it is associated with a significant reduction in urate excretion capacity.[5], [12] Variants rs4148155 and rs74904971 further contribute to the genetic variability in ABCG2function, impacting individual differences in urate handling. Similarly, theSLC17A1(Solute Carrier Family 17 Member 1) gene, encoding the NPT1 transporter, also plays a role in urate transport within the kidney.[5] The missense variant rs1165196 (T269I) in exon 7 of SLC17A1has been linked to variations in serum urate levels, suggesting its involvement in the kidney’s ability to process urate.[5] Other variants like rs1165199 and rs1359232 within SLC17A1may also modulate this transporter’s activity and contribute to the overall genetic influence on urate metabolism.
Beyond these primary urate transporters, several other genes and their variants have been implicated in various physiological processes that can indirectly affect urate levels or are associated with related traits. For example,SLC17A4 (Solute Carrier Family 17 Member 4) belongs to the same family as SLC17A1 and SLC17A3, suggesting a potential, albeit less direct, role in solute transport, which may include urate or related molecules. Variants likers3799340 , rs12212049 , and rs2275906 in SLC17A4 could influence the efficiency of these transport mechanisms. Genes such as WDR1 (WD Repeat Domain 1), PKD2(Polycystic Kidney Disease 2),EVA1CP1 (Eva-1 Homolog C Pseudogene 1), RAF1P1(Raf-1 Proto-Oncogene, Serine/Threonine Kinase Pseudogene 1),CLNK(Cytokine-Like Nuclear Factor), andTSGA10IP (Testis Specific 10 Interacting Protein) have variants like rs717614 in WDR1 or rs2725234 in PKD2that may influence cellular processes, kidney function, or metabolic pathways that indirectly intersect with urate regulation. While their direct impact on urate is not as pronounced asSLC2A9 or ABCG2, these variants may contribute to the polygenic architecture of urate levels or be associated with overlapping health traits.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs1165199 rs1165196 rs1359232 | SLC17A1 | X-13866 urate gout |
| rs2231142 rs4148155 rs74904971 | ABCG2 | urate uric acid trait in response to allopurinol, uric acid gout gout, hyperuricemia |
| rs1850733 rs3775947 rs11722228 | SLC2A9 | urate |
| rs717614 rs34193855 rs573375700 | WDR1 | urate |
| rs2725234 rs544951435 rs748920607 | PKD2 | urate coffee consumption |
| rs13121465 rs13128435 | Metazoa_SRP - EVA1CP1 | urate |
| rs3799340 rs12212049 rs2275906 | SLC17A4 | urate alpha-CEHC sulfate urinary metabolite vanillic acid glycine |
| rs74534386 rs74475455 rs4697939 | WDR1 - RAF1P1 | urate |
| rs2108878 rs2868941 rs997219 | CLNK | urate |
| rs9795139 | DRAP1 - TSGA10IP | uric acid urate |
Urate: Definition and Core Terminology
Section titled “Urate: Definition and Core Terminology”Urate, the ionized form of uric acid, represents the final product of purine metabolism in humans. Its concentration in biological fluids, particularly “plasma uric acid levels” and “serum urate” (SUA), serves as a crucial physiological measure.[8]Elevated levels are associated with various health conditions, highlighting its significance as a “biomarker of cardiovascular disease”.[9]The precise definition of urate as a trait involves quantifying its presence in bodily fluids, establishing a foundational understanding for both clinical diagnosis and research.
Methodologies and Operational Criteria
Section titled “Methodologies and Operational Criteria”The of urate relies on specific methodologies and operational definitions to ensure accuracy and comparability across studies. Common approaches include “serum-urate measurements” and “plasma uric acid levels,” often obtained from “nonfasting samples”.[9] For comprehensive assessment of excretion, “complete 24 hr urine collections” are also utilized.[9] Standardization is critical, with measurements typically performed by specialized facilities like the “Clinical Biochemistry Unit at the University of Glasgow,” which also establishes “normal ranges” for interpretation.[9]Factors such as body mass index (BMI), gender, and age at the time of are routinely considered.[10]alongside “UA-affecting concomitant medications” like diuretics and urate-lowering drugs.[10]which can significantly influence observed urate levels.
Clinical Classification and Associated Factors
Section titled “Clinical Classification and Associated Factors”Urate levels are often classified based on their deviation from established “normal ranges,” which informs clinical diagnosis and risk assessment. Populations can be stratified by characteristics such as BMI into groups like “obese individuals (BMI>35kg/m2)” and “normal weight (BMI<25kg/m2)” to study variations in “plasma uric acid” distribution.[8]Furthermore, genetic factors play a significant role in urate regulation; for instance, theABCG2(BCRP) gene has been identified as an allopurinol transporter and a determinant of drug response, influencing how individuals process urate-lowering medications.[10]The clinical significance of urate extends to its role as a “biomarker” for conditions such as “cardiovascular disease,” necessitating careful monitoring and interpretation of its levels in diverse patient populations.[9]
Urate Metabolism and its Molecular Basis
Section titled “Urate Metabolism and its Molecular Basis”Uric acid, commonly referred to as urate, represents the final product of purine metabolism in humans. This complex metabolic pathway involves both the synthesis of purines, which are fundamental components of nucleic acids like DNA and RNA, and their subsequent breakdown from cellular turnover. The body’s endogenous metabolic processes are significant determinants of circulating uric acid levels. A unique aspect of human physiology is the absence of the enzyme uricase. In many other species, uricase converts uric acid into allantoin, a more soluble compound that is easier to excrete. This enzymatic deficiency in humans means that uric acid remains the terminal product of purine catabolism, making its solubility and efficient elimination critical for maintaining physiological balance.[5]
Renal Urate Homeostasis
Section titled “Renal Urate Homeostasis”The kidneys are the primary organs responsible for regulating systemic urate concentrations through a finely tuned balance of excretion and reabsorption. These processes predominantly occur within the proximal renal tubules, where specialized molecular transport systems facilitate the movement of urate between the blood and the filtered fluid. The net effect of these cellular functions—urate secretion into the tubules and its subsequent reabsorption back into the bloodstream—determines the amount of urate ultimately eliminated in the urine. An imbalance in these mechanisms, particularly an increase in reabsorption or a decrease in secretion, can lead to elevated serum uric acid levels. While extensive research has been conducted, the precise molecular mechanisms governing urate transport in the proximal renal tubules, influencing both secretion and reabsorption, are not yet fully elucidated.[5] Understanding these regulatory networks and the critical proteins involved holds significant research and clinical implications.
Genetic Regulation of Urate Levels
Section titled “Genetic Regulation of Urate Levels”Genetic factors play a substantial role in determining an individual’s serum uric acid concentration. Studies have shown that the heritability of serum uric acid levels is approximately 63%, indicating a strong genetic component to this trait. Genetic variations can influence these levels by affecting the function and expression of genes involved in urate metabolism and transport pathways. These genetic effects may manifest through alterations in regulatory elements that control gene expression patterns, leading to modified levels or activity of key enzymes and transporters. Identifying specific genetic loci associated with urate concentration is vital for unraveling the underlying biological mechanisms and for developing targeted approaches to manage urate-related conditions.[5]
Pathophysiological Consequences of Urate Dysregulation
Section titled “Pathophysiological Consequences of Urate Dysregulation”Disruptions in urate homeostasis can lead to several pathophysiological conditions, most notably hyperuricemia, characterized by abnormally high levels of uric acid in the blood. Hyperuricemia is a well-established primary risk factor for gout, a debilitating inflammatory arthritis resulting from the deposition of urate crystals in joints and surrounding tissues. Impaired renal excretion of urate is a significant factor contributing to the majority of cases of hyperuricemia and gout, highlighting a critical homeostatic imbalance in kidney function. Beyond genetic predispositions, several environmental and lifestyle factors are known to influence urate levels and increase the risk of gout, including obesity, hypertension, the use of certain diuretics, and alcohol consumption.[5]These factors can interact with an individual’s genetic makeup to exacerbate the dysregulation of urate metabolism and transport, leading to systemic consequences and increased disease susceptibility.
Diagnostic Utility and Risk Stratification
Section titled “Diagnostic Utility and Risk Stratification”Urate levels are fundamental for the diagnosis of hyperuricemia, which is clinically defined by serum urate concentrations exceeding 0.4 mMol/l.[9]Genetic predisposition plays a significant role in determining individual urate levels, with variants in genes likeSLC2A9, a glucose transporter, strongly associated with serum urate.[9]This genetic influence, confirmed in diverse cohorts, indicates that individuals carrying specific common alleles have a nearly two-fold increased odds of developing hyperuricemia, offering a pathway for early risk stratification and potentially personalized preventive strategies.[9]
Prognostic Value and Comorbidity Assessment
Section titled “Prognostic Value and Comorbidity Assessment”Serum urate serves as a crucial biomarker with prognostic implications, especially concerning cardiovascular disease and metabolic comorbidities.[9]Research indicates a notable association between elevated urate levels and dyslipidemia, where specific genetic loci nearPSRC1 and CELSR2 are linked to increased nonfasting LDL cholesterol levels.[9]This mechanistic link suggests that urate levels can contribute to risk assessment for coronary disease, offering valuable insights into long-term outcomes and informing comprehensive management strategies for patients with overlapping metabolic phenotypes.[9]
Guiding Treatment and Personalized Medicine
Section titled “Guiding Treatment and Personalized Medicine”Urate levels are essential for guiding therapeutic interventions and optimizing treatment response, particularly for urate-lowering drugs like allopurinol.[10] Genetic factors, such as the ABCG2 gene (BCRP), are recognized as determinants of allopurinol transport and overall drug efficacy.[10]Therefore, monitoring urate levels allows clinicians to personalize allopurinol dosages and account for the impact of concomitant medications, including diuretics or other urate-lowering therapies, ensuring effective management while minimizing adverse effects.[10]
Purine Metabolism and Urate Generation
Section titled “Purine Metabolism and Urate Generation”Uric acid represents the final product of purine catabolism in humans, a crucial metabolic pathway involving the breakdown of nucleic acids from both endogenous cell turnover and dietary sources. This metabolic journey culminates in xanthine, which is then converted to uric acid by the enzyme xanthine oxidase. Unlike many other mammals, humans naturally lack the enzyme uricase, which would otherwise metabolize uric acid into a more soluble and readily excretable compound called allantoin.[5]Consequently, uric acid levels are primarily determined by the balance between its endogenous production, influenced by overall purine biosynthesis and cellular degradation, and its subsequent elimination from the body.[5]The absence of uricase means that the human body relies heavily on renal mechanisms to maintain urate homeostasis, making these processes central to understanding serum urate concentrations.[5]
Renal Handling of Urate
Section titled “Renal Handling of Urate”The kidney plays a paramount role in regulating serum urate levels through a complex interplay of filtration, reabsorption, and secretion in the renal tubules, predominantly the proximal tubules.[5]While urate is freely filtered at the glomerulus, a significant portion is reabsorbed, and some is also actively secreted, resulting in a net excretion that is critical for maintaining systemic balance. Dysregulation in these renal transport mechanisms, particularly an imbalance favoring reabsorption or impaired secretion, is a major contributor to hyperuricemia and, subsequently, the development of gout.[5]Despite extensive research, the precise molecular mechanisms governing urate transport in the proximal renal tubules, which dictate the rates of secretion and reabsorption, are still not fully elucidated.[5]
Genetic and Environmental Modulators of Urate Homeostasis
Section titled “Genetic and Environmental Modulators of Urate Homeostasis”Serum urate levels exhibit a strong genetic component, with studies indicating a substantial heritability of approximately 63%, underscoring the significant influence of genetic variation on individual urate concentrations.[5]This genetic predisposition suggests that variations in genes encoding purine metabolic enzymes, urate transporters in the kidney, or regulatory elements that control their expression can profoundly impact urate homeostasis.[5]Beyond genetics, various environmental and lifestyle factors interact with these pathways, including obesity, hypertension, diuretic use, and alcohol consumption, all of which are recognized risk factors for hyperuricemia and gout.[5]These factors likely modulate urate levels through complex interactions with metabolic and renal regulatory mechanisms, potentially affecting transporter activity, metabolic flux, or inflammatory responses that influence urate handling.[5]
Pathophysiological Consequences and Therapeutic Targets
Section titled “Pathophysiological Consequences and Therapeutic Targets”The intricate balance of urate production and excretion is crucial for health, as its dysregulation leads to hyperuricemia, a primary risk factor for gout, an inflammatory arthritis characterized by urate crystal deposition.[5]The mechanisms underlying hyperuricemia often involve either an overproduction of uric acid from purine metabolism or, more commonly, an underexcretion by the kidneys.[5]Understanding the specific pathways and molecular components, particularly those involved in renal urate transport, offers critical insights for identifying therapeutic targets. Modulating the activity of key urate transporters or enzymes involved in purine metabolism could provide effective strategies for managing hyperuricemia and preventing gout, thereby addressing a significant public health concern.[5]
Frequently Asked Questions About Urate
Section titled “Frequently Asked Questions About Urate”These questions address the most important and specific aspects of urate based on current genetic research.
1. Why does eating certain foods cause me problems but not my friends?
Section titled “1. Why does eating certain foods cause me problems but not my friends?”Your body’s unique genetic makeup influences how it processes purines from food. While purine-rich foods and sugary drinks generally raise urate, specific genes likeGLUT9 affect how your kidneys handle it. This means your genetic background can make you more sensitive to dietary influences than others.
2. My dad has gout; will I definitely get it too?
Section titled “2. My dad has gout; will I definitely get it too?”Not necessarily, but your risk is higher. Genetic factors significantly influence urate levels, and a family history of gout suggests you might have inherited some of these predispositions. However, lifestyle choices like diet also play a big role, so you can take steps to manage your risk.
3. Why are the “high urate” numbers different for men and women?
Section titled “3. Why are the “high urate” numbers different for men and women?”Yes, the thresholds for hyperuricemia are different because of physiological distinctions between sexes. For men, levels above 7.5 mg/dl are typically considered high, while for women, it’s above 6.2 mg/dl. These distinctions reflect general population patterns and risk factors.
4. Do I really need to fast before my urate blood test?
Section titled “4. Do I really need to fast before my urate blood test?”Yes, fasting is important for an accurate result. To ensure the most reliable , blood samples are usually collected in the morning after you’ve fasted for at least 12 hours. This helps standardize the conditions and minimizes fluctuations from recent food intake.
5. Can my daily habits, like sugary drinks, really affect my urate?
Section titled “5. Can my daily habits, like sugary drinks, really affect my urate?”Absolutely. Lifestyle modifications, including dietary changes like reducing purine-rich foods and sugary drinks, are known to influence your urate levels. These environmental factors interact with your genetic predispositions to determine your overall risk.
6. Does my urate level affect my kidneys or heart long-term?
Section titled “6. Does my urate level affect my kidneys or heart long-term?”Yes, persistently high urate levels (hyperuricemia) are linked to several serious health conditions. Beyond gout, they increase your risk for kidney stones, chronic kidney disease, hypertension, metabolic syndrome, and cardiovascular disease over time.
7. Does my family background mean I’m more at risk for high urate?
Section titled “7. Does my family background mean I’m more at risk for high urate?”It can. Genetic studies show that findings from one population might not directly apply to more diverse groups. Your specific ethnic or ancestral background can have different genetic architectures affecting urate levels, so ancestry-specific research is important.
8. Is one blood test enough to know my true urate level?
Section titled “8. Is one blood test enough to know my true urate level?”A single provides a snapshot, but your urate levels can fluctuate. While efforts are made to standardize sample collection, a single time-point might not fully capture the dynamic nature of urate throughout the day. Your doctor might recommend repeat tests if there’s concern.
9. Can medications I take for other things affect my urate?
Section titled “9. Can medications I take for other things affect my urate?”Yes, various medications can influence your urate levels. Environmental factors, including medication use, are known to substantially affect urate. It’s important to discuss all your medications with your doctor, as they may need to be considered when interpreting your results.
10. Why do some people never get gout even with a bad diet?
Section titled “10. Why do some people never get gout even with a bad diet?”It comes down to a complex interplay of genetics and environment. While diet is a factor, individuals have different genetic predispositions that affect how their bodies produce and excrete urate. Some people simply have a genetic makeup that makes them less susceptible, even with similar lifestyle choices.
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] Li S, et al. “The GLUT9gene is associated with serum uric acid levels in Sardinia and Chianti cohorts.” PLoS Genet, 2007.
[2] Carvalho BS, Louis TA, Irizarry RA. “Quantifying uncertainty in genotype calls.” Bioinformatics, 2010.
[3] Karns R et al. “Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia.” Ann Hum Genet. 2012.
[4] Aringer M, McKeigue PM, Ralston SH, Morris AD, Rudan P, Hastie ND, Campbell H, Wright AF. “SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout.” Nat Genet. 2008.
[5] Dehghan A et al. “Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study.” Lancet. 2008.
[6] Yang B et al. “A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population.” BMC Med Genomics. 2014.
[7] Kolz M et al. “Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations.” PLoS Genet. 2009.
[8] Li, WD. “A genome wide association study of plasma uric acid levels in obese cases and never-overweight controls.”Obesity (Silver Spring), 2013. PMID: 23703922.
[9] Wallace C, Newhouse SJ, Braund P, Zhang F, Tobin M, Falchi M, Ahmadi K, Dobson RJ, Marçano AC, Hajat C, Burton P, Deloukas P, Brown M, Connell JM, Dominiczak A, Lathrop GM, Webster J, Farrall M, Spector T, Samani NJ, Caulfield MJ, Munroe PB. “Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia.” Am J Hum Genet. 2008.
[10] Wen, C. C., et al. “Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response.” Clin Pharmacol Ther, 2015.