Abstract
Although several risk single nucleotide polymorphisms (SNPs) have been found to play an important role in etiology of irritable bowel syndrome (IBS), the findings are inconsistent. A descriptive correlational design was used to analyze the baseline data of a randomized controlled trial including participants with IBS and healthy controls (HC). Pain severity and interference, anxiety, sleep, and fatigue were measured using the Brief Pain Inventory (BPI) and patient-reported outcomes measurement information system (PROMIS). Fisher’s exact test and multivariate linear regression were used to investigate the associations between IBS risk alleles and IBS symptoms. Participants were predominantly female, white, and had an average age of 21.13 ± 2.42 years. Polymorphisms within TNFSF15 (rs4263839), SLC6A4 5-HTTLPR, HTR3A (rs1062613), and OXTR (rs2254298) were associated with IBS risk, and TNFSF15 (rs4263839), COMT (rs6269), SLC6A4 5-HTTLPR polymorphisms were associated with pain severity. TNFSF15 (rs4263839) and COMT (rs4680; rs4633) genotypes were associated with sleep disturbance, and the ADRA1D SNP rs1556832 was associated with fatigue in both IBS and HC groups. Genotypic differences were associated with IBS risk and symptoms including abdominal pain, sleep disturbance, and fatigue. Further investigation is warranted to reveal the mechanisms by which these genetic variations influence the dynamic nature of IBS symptoms over time.
Highlights
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, with a global prevalence of 7–21% [1,2]
We investigated the association between irritable bowel syndrome (IBS) risk and single nucleotide polymorphisms (SNPs) by checking the difference of distribution of genotypes for each SNP between the IBS and the healthy controls (HC) groups
For all SNPs assessed, we found the control group to be in Hardy-Weinberg Equilibrium (HWE) except for HTR3A rs1062613, while for our phenotype of interest (IBS), two SNPs, HTR3A rs1062613 and Opioid Receptor Mu 1 (OPRM1) rs1799971, were out of HWE
Summary
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, with a global prevalence of 7–21% [1,2]. The genotype of SNP TNFSF15 rs4263839 (located at 9q32) correlated with TNFSF15 mRNA expression was associated with an increased risk of IBS [15,16,20] These genetic polymorphisms alone are not sufficient for the IBS diagnosis, these variations suggest a role of TNFSF15 in the pathology of IBS and the severity of IBS symptoms, e.g., sleep disturbance [21]. The influence of serotoninergic signaling in the etiology of IBS has been further shown from studies indicating an association between hydroxy tryptamine receptor 3A encoding the 5-HT3 receptor (HTR3A) rs1062613 SNP genotype and increased risk of IBS [34]. We selected candidate polymorphisms of TNFSF15 rs4263839, OXTR rs2254298 and rs53576, OPRM1 rs1799971, HTR3A rs1062613, COMT rs4680, rs4818, rs6269, rs4633, and ADRAID rs1556832 as susceptibility loci either related to GI disorders or symptoms such as sleep deprivation, pain, anxiety, and depression [20,21,34–39]. Risk alleles can be considered biological markers of IBS and symptom severity, and future studies can be conducted to develop the putative therapeutic targets
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