Peptic Ulcer
Peptic ulcer disease (PUD) refers to open sores that develop on the inside lining of the stomach (gastric ulcers), the upper part of the small intestine (duodenal ulcers), or less commonly, the esophagus. Historically, peptic ulcers were often attributed to stress or diet, but modern understanding highlights two primary causes: infection with the bacteriumHelicobacter pylori (H. pylori) and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin oscopy and tests for H. pylori. Treatment often includes antibiotics to eradicate H. pylori and acid-suppressing medications, alongside avoiding NSAIDs. Understanding genetic predispositions can help in identifying individuals at higher risk, particularly for NSAID-induced ulcers, allowing for more personalized preventive strategies.
The social importance of peptic ulcer disease is significant due to its global prevalence and potential for serious complications. It imposes a substantial burden on healthcare systems through diagnostic procedures, long-term treatment, and management of acute complications. The chronic nature of the condition and its symptoms can significantly impact an individual’s quality of life. Research into the genetic underpinnings of peptic ulcer disease holds promise for developing more targeted prevention strategies and treatments, ultimately reducing its impact on public health.
Limitations
Section titled “Limitations”Understanding the genetic underpinnings of peptic ulcer disease is an evolving field, and current research, while valuable, operates within several limitations. These considerations are crucial for interpreting findings and guiding future investigations.
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Current studies on peptic ulcer and related digestive disorders often show considerable variability in the sample sizes of case cohorts, ranging from relatively small groups to extensive populations of tens of thousands[1]. This disparity can restrict the statistical power needed to confidently identify subtle genetic associations, particularly for less common conditions or complex genetic effects that involve multiple genes. An imbalance in sample sizes across different disorders within meta-analyses may also increase the likelihood of Type I errors, potentially leading to the detection of associations that are not truly significant [1]. Furthermore, some analyses may rely on broad phenotypic classifications or proxy conditions for peptic ulcer, which, while boosting overall sample size, can reduce the specificity of the genetic signals being investigated[2].
The integration of genetic data, often in the form of summary statistics, from various research cohorts and biobanks can introduce inherent heterogeneity due to differences in data collection protocols, diagnostic criteria, and quality control measures [2]. Although efforts are made to harmonize these diverse datasets, such variations can complicate the interpretation of combined results and affect the reliability of findings across different studies. While replication studies are essential for validating genetic associations, the common practice of selecting a limited number of top variants for replication, even with specific statistical thresholds, means that many potential genetic signals may not be fully confirmed across various populations or study designs [3].
Population Specificity and Phenotype Definition
Section titled “Population Specificity and Phenotype Definition”A notable limitation in the genetic research of peptic ulcer disease is the predominant focus on individuals of European ancestry[1]. This methodological choice, often made to mitigate confounding effects from diverse genetic backgrounds, significantly constrains the applicability of the findings to non-European populations, which may possess distinct genetic architectures or unique environmental exposures influencing peptic ulcer susceptibility[1]. Future research must prioritize the evaluation of these genetic associations in more diverse ancestral groups to establish a comprehensive understanding of peptic ulcer risk globally.
The precise definition and ascertainment of peptic ulcer phenotypes can vary substantially between studies, which may affect the accuracy and interpretability of genetic associations. Utilizing broad diagnostic categories or surrogate conditions, while sometimes necessary for increasing statistical power, may inadvertently mask genetic variants that are specific to particular forms of peptic ulceration, such as those induced by aspirin or primarily caused byHelicobacter pyloriinfection[2]. Inconsistencies in diagnostic criteria, clinical coding, and the inclusion or exclusion of specific ulcer locations (e.g., gastric versus duodenal) across different cohorts can introduce variability and diminish the ability to pinpoint highly specific genetic influences.
Unaccounted Environmental Factors and Etiological Complexity
Section titled “Unaccounted Environmental Factors and Etiological Complexity”Peptic ulcer disease is recognized as a multifactorial condition, strongly influenced by environmental elements such asHelicobacter pyloriinfection, the use of non-steroidal anti-inflammatory drugs (e.g., aspirin), and various lifestyle factors[4]. Although some studies incorporate key covariates like H. pylori status and steroid use into their analytical models, the intricate interplay between genetic predispositions and a broad spectrum of environmental exposures (gene-environment interactions) frequently remains underexplored or inadequately quantified [4]. Unmeasured or residual confounding from these environmental factors can significantly impact the observed genetic associations and contribute to the “missing heritability” that common genetic variants alone cannot fully explain.
Current genetic investigations primarily concentrate on variations in DNA sequence, often overlooking the potential role of epigenetic factors in the development and progression of peptic ulcer disease[1]. These epigenetic modifications could represent an additional layer of regulatory complexity that influences disease susceptibility. Moreover, a substantial proportion of identified genetic signals reside in non-coding regions of the genome, necessitating extensive functional characterization to elucidate their precise biological mechanisms[1]. The current reliance on bioinformatics predictions and public databases for functional insights, without robust experimental validation studies, leaves significant gaps in our understanding of how these genetic variants mechanistically contribute to peptic ulcer disease[1].
Variants
Section titled “Variants”Genetic variants play a significant role in an individual’s susceptibility to peptic ulcer disease (PUD), influencing everything from mucosal integrity to immune responses and gastric acid secretion. Variants likers993258675 in the RAP1GAP2 gene are associated with fundamental cellular processes critical for maintaining the health of the gastrointestinal lining. RAP1GAP2 encodes a GTPase-activating protein that regulates Rap1, a small GTPase crucial for cell adhesion, tight junction formation, and cell polarity, all essential for the epithelial barrier protecting the stomach and duodenum. Compromised Rap1 signaling due to such variants could weaken this barrier, increasing vulnerability to damage from gastric acid and Helicobacter pyloriinfection, a major contributor to PUD[5]. Other genes, such as MUC6, which encodes a mucin protein, are also recognized for their critical role in mucosal protection, with intronic variants like rs78459074 in MUC6 being linked to PUD susceptibility, further highlighting the importance of the mucosal barrier [5].
The genetic landscape of peptic ulcer disease also encompasses variants likers116562357 , spanning the HCG24 and COL11A2 genes, which may impact immune regulation and tissue structural integrity. HCG24 is located within the major histocompatibility complex (MHC) region, a genomic area densely packed with genes vital for immune system function. Variants in this region could modulate the immune response to pathogens like H. pylori or influence the inflammatory processes that contribute to ulcer formation and healing. Adjacent to this, COL11A2 encodes a component of type XI collagen, a key structural protein in connective tissues, including those supporting the gastrointestinal wall. Alterations in collagen structure due to variants could weaken the mechanical resilience of the mucosa, predisposing individuals to ulceration or hindering effective tissue repair. Similarly, the ABO blood group gene, through variants like rs8176719 , and the FUT2 gene, with variants such as rs1047781 , are strongly associated with PUD risk, particularly influencing susceptibility and immune responses to H. pyloriinfection, with blood group O and non-secretor status increasing risk[6].
Cellular adhesion and tissue repair mechanisms are further influenced by genes like CDH4, where variant rs200856094 might play a role in PUD. CDH4, or R-cadherin, is a classical cadherin protein essential for calcium-dependent cell-cell adhesion, critical for maintaining the tight junctions and overall integrity of epithelial tissues. Disruptions in CDH4 function could compromise the protective epithelial barrier, making the gastric or duodenal lining more vulnerable to damage and impeding the coordinated cellular processes required for ulcer healing. Beyond structural integrity, genes involved in gastric acid secretion and neurohormonal regulation also contribute to PUD risk. For example, the CCKBR gene, encoding the cholecystokinin B receptor, is highly expressed in the stomach and brain, regulating gastrin and cholecystokinin—peptides that control gastric acid secretion and gastrointestinal motility [5]. Variations in genes like EYA1 have also been linked to aspirin-induced peptic ulceration, highlighting the diverse genetic pathways that can influence PUD susceptibility [4].
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs993258675 | RAP1GAP2 | peptic ulcer |
| rs116562357 | HCG24 - COL11A2 | peptic ulcer |
| rs200856094 | CDH4 | peptic ulcer |
Causes of Peptic Ulcer
Section titled “Causes of Peptic Ulcer”Peptic ulcer disease (PUD) is a complex disorder influenced by a combination of genetic predispositions, environmental factors, and the intricate interactions between them[5]. The development of PUD is recognized as a multistep process, often involving damage to the gastroduodenal mucosa [5].
Genetic Susceptibility and Shared Pathways
Section titled “Genetic Susceptibility and Shared Pathways”Genetic factors play a significant role in an individual’s susceptibility to peptic ulcer disease, which is considered a polygenic condition[1]. Genome-wide association studies (GWAS) have identified specific genetic variants associated with PUD and its related conditions, highlighting the shared genetic architecture among various digestive disorders [5]. For instance, a genome-wide significant association has been found for the variant rs12678747 , which doubles the risk for aspirin-induced peptic ulceration [4]. Beyond specific single nucleotide polymorphisms (SNPs), polymorphisms in genes likeCYP2C19 (specifically the CYP2C1917 gain-of-function polymorphism) and the cyclooxygenase-1 (COX-1) gene promoter have been linked to peptic ulcer disease, impacting drug metabolism and inflammatory responses[7]. The genetic predisposition to acute gastrointestinal bleeding following NSAID use is also influenced by cytochrome P450 2C9 (CYP2C9) polymorphisms and genes involved in platelet activation and inflammatory responses [8].
Environmental Influences: Infection and Medications
Section titled “Environmental Influences: Infection and Medications”The primary environmental triggers for peptic ulcer disease areHelicobacter pylori (H. pylori) infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin[5]. H. pyloriinfection initiates a multistep process involving inflammation and subsequent damage to the gastric mucosa, which can lead to ulcer formation[5]. NSAIDs, on the other hand, exert their ulcerogenic effect primarily by inhibiting cyclo-oxygenase 1 (COX-1), thereby reducing the production of prostaglandins that are crucial for protecting the gastric mucosa from acid[4]. While NSAID-induced ulceration is largely understood through this mechanism, it also involves multiple other interacting pathways that contribute to tissue injury [4].
Complex Interactions and Comorbidities
Section titled “Complex Interactions and Comorbidities”The development of peptic ulcers often involves complex interactions between an individual’s genetic makeup and environmental exposures. Host factors can influence both the susceptibility to H. pyloriinfection and the subsequent inflammatory response, highlighting a gene-environment interaction[5]. Furthermore, peptic ulcer disease frequently co-occurs with other health conditions, underscoring a broader systemic vulnerability. Studies have implicated other gastrointestinal disorders, such as gastroesophageal reflux disease (GORD) and inflammatory bowel diseases (IBD), as well as depression, in the causal landscape of PUD[5]. Certain medications, beyond NSAIDs, such as steroids, have also been identified as contributing factors in the development of peptic ulcers [4].
Biological Background of Peptic Ulcer
Section titled “Biological Background of Peptic Ulcer”Peptic ulcer disease (PUD) is a common gastrointestinal disorder characterized by breaks, or ulcers, in the inner lining of the digestive tract, typically located in the stomach (gastric ulcers) or the proximal duodenum (duodenal ulcers)[5]. This condition is a complex interplay of environmental factors, genetic predispositions, and disruptions in the delicate balance of protective and aggressive factors within the gastrointestinal mucosa. The primary risk factors for peptic ulcer development are infection withHelicobacter pylori bacteria and the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin [5]. Understanding the intricate biological mechanisms underlying these factors is crucial for prevention and treatment.
Pathophysiological Mechanisms and Key Risk Factors
Section titled “Pathophysiological Mechanisms and Key Risk Factors”Peptic ulcers manifest as lesions in the gastrointestinal lining, primarily affecting the stomach and the initial part of the small intestine, the duodenum [5]. The formation of these ulcers results from an imbalance between aggressive factors, such as gastric acid and pepsin, and defensive factors, including the mucosal barrier, bicarbonate secretion, and prostaglandin production. The two main causes contributing to this imbalance are Helicobacter pyloriinfection and the use of non-steroidal anti-inflammatory drugs (NSAIDs)[5]. NSAIDs, including aspirin, induce ulceration primarily by inhibiting cyclo-oxygenase 1 (COX-1), an enzyme essential for the synthesis of prostaglandins[4]. These prostaglandins are vital biomolecules that maintain gastric mucosal integrity, regulate blood flow, and inhibit acid secretion, making their reduction a significant factor in compromising the stomach’s protective barrier and increasing its vulnerability to acid damage[4]. The mechanism of NSAID-induced peptic ulceration is complex and involves multiple interacting pathways beyond just mucosal protection, encompassing various types such as gastric, duodenal, and aspirin-induced ulcers [4].
Molecular and Cellular Pathways of Mucosal Integrity
Section titled “Molecular and Cellular Pathways of Mucosal Integrity”At a molecular level, the integrity of the gastrointestinal mucosa is maintained by a delicate balance of cellular functions and signaling pathways. NSAIDs disrupt this balance by inhibiting the enzyme cyclo-oxygenase 1 (COX-1), which is crucial for the production of prostaglandins[4]. Prostaglandins are lipid compounds that play a protective role in the stomach by enhancing mucus and bicarbonate secretion, maintaining mucosal blood flow, and suppressing gastric acid output. Their deficiency, resulting from COX-1 inhibition, leaves the gastric lining vulnerable to damage from stomach acid and digestive enzymes[4]. Furthermore, the metabolism of NSAIDs itself involves cytochrome P450 enzymes, such as CYP2C9 and CYP2C19. Genetic polymorphisms in these enzymes can influence drug metabolism rates, thereby altering an individual’s susceptibility to NSAID-induced gastrointestinal bleeding and ulceration [9]. Beyond these direct effects, inflammatory responses also contribute to ulcer pathogenesis, involving molecular mediators and pathways like cytokine-cytokine receptor interactions, leukocyte activation, and other immune effector processes[10].
Genetic Contributions and Regulatory Networks
Section titled “Genetic Contributions and Regulatory Networks”Genetic factors play a significant role in determining an individual’s susceptibility to peptic ulcer disease and its complications. For instance, specific genetic polymorphisms within the promoter region of the cyclooxygenase-1 gene have been associated with peptic ulcer development, influencing the expression and activity of this critical enzyme[11]. The EYA1 gene has also been implicated in aspirin-induced peptic ulceration, highlighting specific genetic predispositions to drug-induced forms of the disease[4]. Variations in drug-metabolizing enzymes are particularly important, with the CYP2C19*17 gain-of-function polymorphism linked to an increased risk of peptic ulcer disease, and specific CYP2C9 genotypes influencing susceptibility to NSAID-induced gastric ulceration and bleeding[7]. Genome-wide association studies (GWAS) have revealed a complex genetic architecture for peptic ulcer disease, indicating shared genetic variants and regulatory networks with other gastrointestinal disorders such as gastro-esophageal reflux disease (GORD), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and even depression[5]. Functional analyses like Gene Ontology (GO) and KEGG pathway enrichment help to elucidate the biological mechanisms of these pleiotropic genetic loci, often pointing to roles in immune response regulation and inflammatory pathways [1].
Systemic and Organ-Level Interactions
Section titled “Systemic and Organ-Level Interactions”While peptic ulcers are localized lesions primarily affecting the stomach and duodenum, their occurrence and progression are influenced by and can impact the broader physiological context of the body. Peptic ulcer disease is a highly prevalent condition that contributes to substantial healthcare resource utilization, imposes a significant societal economic burden, and negatively impacts the quality of life for affected individuals[5]. Research indicates that peptic ulcer disease often correlates with other gastrointestinal disorders, including gastro-esophageal reflux disease (GORD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD)[5]. This suggests a commonality in underlying pathophysiological processes or shared risk factors across these conditions. Furthermore, genetic studies have revealed a shared genetic architecture not only among various digestive disorders but also with seemingly unrelated conditions like lung diseases [10]. These intricate interconnections at the organ and systemic levels underscore the complex nature of peptic ulcer disease, reflecting how local tissue injury can be part of a broader network of physiological and genetic interactions across different organ systems[5].
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Peptic ulcer disease involves a complex interplay of genetic predispositions, specific pathogenic triggers, and dysregulated host responses, manifesting through several interconnected molecular pathways. These mechanisms collectively contribute to the imbalance between aggressive factors, such as acid and pepsin, and defensive factors like mucus, bicarbonate, and prostaglandin production, leading to mucosal erosion.
Genetic Predisposition and Gene Regulatory Networks
Section titled “Genetic Predisposition and Gene Regulatory Networks”Genetic factors play a significant role in individual susceptibility to peptic ulcer disease, influencing how genes are expressed and regulated. Genome-wide association studies (GWAS) have identified specific genetic variants associated with peptic ulceration, including a strong association between theEYA1 gene and aspirin-induced peptic ulceration [4]
Immune and Inflammatory Signaling Pathways
Section titled “Immune and Inflammatory Signaling Pathways”A central pathway in peptic ulcer pathogenesis, particularly for duodenal ulcers, is the host’s immune and inflammatory response toHelicobacter pyloriinfection[5]
Cellular Homeostasis and Stress Response
Section titled “Cellular Homeostasis and Stress Response”Maintaining cellular homeostasis and mounting an effective stress response are crucial for protecting the gastrointestinal mucosa from damage. Peptic ulceration often results from a failure in these protective mechanisms, whether due to infection, medication, or other stressors. The cellular response to stress, including the positive regulation of multicellular organismal processes and general cell activation, is vital for tissue repair and regeneration[10]
Systems-Level Integration and Cross-Disorder Interactions
Section titled “Systems-Level Integration and Cross-Disorder Interactions”Peptic ulcer disease does not exist in isolation but is often interconnected with other gastrointestinal and systemic disorders, reflecting a systems-level integration of shared biological pathways and genetic architectures. Studies have revealed shared genetic variants and genes across various digestive disorders, indicating significant pathway crosstalk and network interactions[1]
Pharmacogenetics of Peptic Ulcer
Section titled “Pharmacogenetics of Peptic Ulcer”Pharmacogenetic Modulators of Drug Metabolism and Efficacy
Section titled “Pharmacogenetic Modulators of Drug Metabolism and Efficacy”Genetic variations in drug-metabolizing enzymes significantly influence the pharmacokinetics and safety of medications associated with peptic ulcer. Polymorphisms in cytochrome P450 2C9 (CYP2C9), for instance, are associated with an increased risk of nonsteroidal anti-inflammatory drug (NSAID)-related gastroduodenal bleeding.[12]These variants can lead to altered drug metabolism, resulting in higher systemic drug exposure and increased gastrointestinal toxicity for many commonly used NSAIDs. Similarly, the CYP2C19*17 gain-of-function polymorphism has been linked to peptic ulcer.[7] This variant may affect drug efficacy or susceptibility to ulceration through mechanisms involving altered drug activation or detoxification pathways. The overall metabolic phenotype, shaped by these and other phase II enzymes, plays a crucial role in determining the pharmacokinetic profile of drugs, impacting both their therapeutic effectiveness and the likelihood of adverse reactions.
Genetic Determinants of Drug Target Response and Disease Susceptibility
Section titled “Genetic Determinants of Drug Target Response and Disease Susceptibility”Genetic variations affecting drug targets and inflammatory pathways contribute to an individual’s susceptibility to peptic ulcer and their response to treatment. Polymorphisms in the cyclooxygenase-1 (COX-1) gene promoter are associated with peptic ulcers.[11] Given that COX-1 inhibition is a primary mechanism for NSAID-induced ulceration, such variants can modify an individual’s risk of gastrointestinal injury from NSAIDs. Furthermore, polymorphisms involved in platelet activation and inflammatory responses influence the risk of aspirin-related upper gastrointestinal bleeding. [13] These genetic differences can alter critical signaling pathways for mucosal protection and repair, thereby modulating the pharmacodynamic effects of drugs like aspirin. A genome-wide association study identified a significant association between rs12678747 , located near the EYA1 gene, and aspirin-induced peptic ulceration, highlighting specific genetic predispositions to adverse drug reactions. [4]Beyond drug-related effects, genetic associations with peptic ulcer also implicateHelicobacter pyloriinfection, suggesting that host genetic factors can influence susceptibility to infection-induced ulcers.[5]
Translating Pharmacogenomics into Clinical Practice
Section titled “Translating Pharmacogenomics into Clinical Practice”Integrating pharmacogenomic insights into clinical practice offers a path toward personalized management of peptic ulcer. Understanding an individual’s genetic profile, particularly concerning drug-metabolizing enzymes like CYP2C9, could guide drug selection or dose adjustments for NSAIDs to reduce the risk of gastrointestinal bleeding.[12]Similarly, identifying genetic variants in drug targets such as COX-1 or in genes related to platelet activation could inform prescribing decisions for aspirin or other anti-inflammatory agents. While the evidence for some pharmacogenetic associations, such as those involving CYP2C9, is robust, the routine implementation of broad pharmacogenetic testing for peptic ulcer risk is still developing. The clinical utility of these genetic markers lies in their potential to minimize adverse drug reactions and optimize treatment outcomes through personalized prescribing, necessitating ongoing research to establish comprehensive clinical guidelines for their routine integration.
Frequently Asked Questions About Peptic Ulcer
Section titled “Frequently Asked Questions About Peptic Ulcer”These questions address the most important and specific aspects of peptic ulcer based on current genetic research.
1. My dad had ulcers; will I get them too?
Section titled “1. My dad had ulcers; will I get them too?”Yes, you might have a higher risk. Genetics play a role in your susceptibility to peptic ulcers, influencing factors like your stomach lining’s vulnerability or your response to H. pyloriinfection. While it’s not a guarantee, your family history suggests you should be mindful of risk factors like NSAID use.
2. I take a lot of aspirin for pain; am I more at risk for ulcers than my friends?
Section titled “2. I take a lot of aspirin for pain; am I more at risk for ulcers than my friends?”Yes, your genetics can influence your risk even if you take aspirin often. Variations in genes like EYA1 have been linked to aspirin-induced ulcers, and other genes, such as cytochrome P450 2C9, can affect how your body processes NSAIDs. This means some individuals are genetically more sensitive to NSAID-induced stomach damage.
3. Why did I get H. pylori ulcers, but my partner didn’t, even though we were both exposed?
Section titled “3. Why did I get H. pylori ulcers, but my partner didn’t, even though we were both exposed?”Even with exposure to H. pylori, your genetics can make you more susceptible to developing ulcers. Certain genetic variations influence how your body reacts to the infection and the strength of your stomach’s protective barrier. This can lead to inflammation and damage in some individuals, but not others.
4. I always thought stress caused ulcers; is that still true?
Section titled “4. I always thought stress caused ulcers; is that still true?”While stress isn’t a primary direct cause like H. pylori or NSAIDs, the connection is more complex than previously thought. Genetic studies have found links between ulcer risk and genes associated with conditions like depression. So, while stress alone might not directly cause an ulcer, your genetic background can influence how related factors affect your overall risk.
5. I have Inflammatory Bowel Disease (IBD); does that mean I’m more likely to get ulcers?
Section titled “5. I have Inflammatory Bowel Disease (IBD); does that mean I’m more likely to get ulcers?”Yes, you might have an increased risk. Research shows shared genetic factors, or “shared genetic architecture,” between peptic ulcer disease and other gastrointestinal disorders like IBD. This means you may carry genetic variations that predispose you to both conditions due to common biological pathways.
6. Can knowing my specific genetics help me prevent ulcers?
Section titled “6. Can knowing my specific genetics help me prevent ulcers?”Yes, absolutely. Understanding your genetic predispositions can help identify if you’re at a higher risk, especially for ulcers caused by NSAIDs. This information allows doctors to recommend more personalized prevention strategies, such as avoiding certain medications or closer monitoring, tailored to your unique genetic profile.
7. Does my specific ethnic background affect my ulcer risk?
Section titled “7. Does my specific ethnic background affect my ulcer risk?”It’s possible, but current research has limitations. Most genetic studies on ulcers have focused predominantly on individuals of European ancestry. This means we don’t fully understand the unique genetic risk factors in non-European populations, which may have distinct genetic architectures influencing susceptibility.
8. Why do some people seem to get ulcers easily, but others never do, despite similar habits?
Section titled “8. Why do some people seem to get ulcers easily, but others never do, despite similar habits?”It often comes down to individual susceptibility, which is partly genetic. Some people naturally have a more robust protective stomach lining or a different immune response to H. pylori, making them more resilient. Your genes influence this delicate balance between aggressive factors and protective mechanisms in your stomach.
9. Can my ulcer risk be linked to other health issues I have, like lung problems?
Section titled “9. Can my ulcer risk be linked to other health issues I have, like lung problems?”Yes, definitely. There’s evidence of shared genetic links, known as pleiotropy, between peptic ulcer disease and various other conditions, including other digestive disorders, IBD, and even lung function. This means that genetic factors predisposing you to one condition might also increase your risk for ulcers.
10. Why do NSAIDs give me stomach issues or bleeding, but not my friend?
Section titled “10. Why do NSAIDs give me stomach issues or bleeding, but not my friend?”Your body’s genetic makeup can significantly influence how you react to NSAIDs. For instance, variations in genes like cytochrome P450 2C9 can affect how your body metabolizes these drugs, impacting your risk of gastrointestinal side effects or bleeding. This means some people are inherently more sensitive to NSAID-induced damage due to their genes.
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] Jiang, M., et al. “Genetic and observational associations of lung function with gastrointestinal tract diseases: pleiotropic and mendelian randomization analysis.” Respir Res, vol. 24, no. 1, 2023, p. 288. PMID: 38102678.
[2] Adewuyi, E. O. et al. “A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and gastrointestinal tract disorders.”Commun Biol, vol. 5, no. 1, 2022.
[3] Manry, J., et al. “Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway.” Communications Biology, vol. 3, 2020, p. 177.
[4] Bourgeois, S. et al. “Genome-Wide association between EYA1 and Aspirin-induced peptic ulceration.” EBioMedicine, 2021. PMID: 34864618.
[5] Wu, Y. et al. “GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression.”Nat Commun, vol. 12, no. 1, 2021, p. 1146. PMID: 33608531.
[6] He, Y. et al. “East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease.”Nat Genet, 2023. PMID: 38036781.
[7] Musumba, C. O., et al. “CYP2C19*17 gain-of-function polymorphism is associated with peptic ulcer disease.” *Clinical Pharmacology & Therapeutics*, vol. 93, no. 2, 2013, pp. 195–203.
[8] Martinez, C. et al. “Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use.” Br J Pharmacol, vol. 141, no. 2, 2004, pp. 205–8.
[9] Macias, Y., et al. “An update on the pharmacogenomics of NSAID metabolism and the risk of gastrointestinal bleeding.” Expert Opin Drug Metab Toxicol, vol. 16, no. 4, 2020, pp. 319-32.
[10] You, D., et al. “A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases.” Nature Communications, vol. 16, 2025, p. 3032. PMID: 40155373.
[11] Arisawa, T. et al. “Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan.” Int J Mol Med, vol. 20, no. 3, 2007, pp. 373–8.
[12] Pilotto, A. et al. “Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms.” Gastroenterology, vol. 133, no. 2, 2007, pp. 465–71.
[13] Mallah, N. et al. “Influence of polymorphisms involved in platelet activation and inflammatory response on aspirin-related upper gastrointestinal bleeding: a case-control study.” Front Pharmacol, vol. 11, 2020, p. 860.