Association Between SLC6A4 Serotonin Transporter Gene Lainked Polymorphic Region and ADRA2A −1291C>G and Irritable Bowel Syndrome in Korea

Abstract

Background/AimsDespite numerous studies on the relation of genetic polymorphisms with irritable bowel syndrome (IBS), the results still remain inconclusive. The aim of this study was to assess the possible association between SLC6A4 serotonin transporter gene linked polymorphic region (5-HTTLPR), ADRA2A −1291C>G, GNB3 825C>T, CCK1R intron 779T>C and TRPV1 945G>C polymorphisms and IBS based on Rome III criteria in Korea. MethodsStudy subjects were prospectively recruited from visitors to Seoul National University Bundang Hospital between July 2009 and January 2014. Ninety-nine IBS patients and 171 healthy controls were enrolled. Polymorphisms of above-mentioned 5 genes were genotyped. Serum serotonin from 101 participants was measured by ELISA and compared according to SLC6A4 5-HTTLPR polymorphisms and IBS subtypes. ResultsRegarding SLC6A4 5-HTTLPR polymorphism, L/L genotype was significantly associated with the total IBS, constipation predominant IBS (IBS-C) and mixture of diarrhea and constipation IBS (IBS-M) (adjusted OR: 4.35, 95% CI: 1.04-16.67; adjusted OR: 11.11, 95% CI: 1.69-50.00 and adjusted OR: 5.56, 95% CI: 1.05-33.33, respectively). Carrying ADRA2A −1291G allele was significantly associated with total IBS and diarrhea predominant IBS (adjusted OR: 3.37, 95% CI: 1.16-9.77 and adjusted OR: 5.64, 95% CI: 1.18-27.01, respectively). IBS-C patients showed reduced level of serum serotonin compared to controls and patients with diarrhea predominant IBS (50.2 ng/mL vs. 69.0 ng/mL and 92.9 ng/mL, P = 0.017 and P = 0.001, respectively).

Sex-Gender Differences in Irritable Bowel Syndrome

“…123 Recently, we published that IBS is related to SLC6A4 5-HTTLPR polymorphism. 124 That is, the L/L genotype was significantly associated with total IBS, IBS-C, and IBS alternating between diarrhea and constipation. 124 In addition, IBS-C patients showed reduced levels of serum serotonin compared to controls and IBS-D patients (P = 0.001).…”

“…124 That is, the L/L genotype was significantly associated with total IBS, IBS-C, and IBS alternating between diarrhea and constipation. 124 In addition, IBS-C patients showed reduced levels of serum serotonin compared to controls and IBS-D patients (P = 0.001). 123 Interestingly, the 5-HT signaling differences between women and men have been suggested to be associated with the effectiveness of 5-HT 3 receptor antagonists.…”

Expression of Neurotrophic Factors, Tight Junction Proteins, and Cytokines According to the Irritable Bowel Syndrome Subtype and Sex

“…A validated Rome III criteria-based bowel disease questionnaire was translated from the original Bowel Disease Questionnaire into Korean (Korean Bowel Disease Questionnaire) and used to investigate patient's bowel symptoms. 18,19 Patients were asked to rate frequency and severity of symptoms experienced over the last 3 months prior to the study. The severity of abdominal pain was scored from 1 to 5 according to its impact on patients' daily activities: 1, mild; 2, relevant; 3, moderate; 4, severe; and 5, extremely severe.…”

Functional polymorphism of the serotonin reuptake transporter SLC6A4 gene in various clinical variants of irritable bowel syndrome

“…Choi и соавт. [46]. Вместе с тем в исследованиях, проведенных в популяциях Юго-Восточного Ирана, Северной Индии, фенотип СРК-З значительно чаще встречался у пациентов с генотипами SS и L/S гена SLC6A4 по сравнению с СРК-Д и смешанной формой СРК [47,48].…”