The Role of 5-HTT LPR and GNβ3 825C>T Polymorphisms and Gene–Environment Interactions in Irritable Bowel Syndrome (IBS)
- 300 Downloads
Smaller studies have evaluated SLC6A4 5-HTTLPR and GNβ3 825C>T polymorphisms in IBS, and interactions between 5-HTT LPR with life events have been reported in the psychiatric literature, but gene–environment studies in IBS are lacking.
The purpose of this study was to assess the association of two polymorphisms with IBS and age of onset, and whether there are gene–environment interactions with IBS.
Outpatients with IBS and controls completed a validated questionnaire and provided blood for DNA. Comparisons of genotype/allele frequencies between cases and controls were performed with logistic regression. Linear regression was used to evaluate the association between the variants and age of onset. Environmental variables tested included abuse, parental alcohol abuse, parental psychiatric disorders, and gastrointestinal infections.
Genotyping was performed in 385 cases and 262 controls with median age of 50 years (range, 18.0–70.0) and 498 (77 %) females. The IBS subtype distribution among cases was: 102 (26 %) D-IBS, 40 (10 %) C-IBS, 125 (32 %) M-IBS, 118 (31 %) other. No association was observed between IBS or age of onset and both variants. Significant interactions were observed between GI infection and the GNβ3 825T allele. For those reporting gastrointestinal infection, the OR for IBS was 3.9 (95 % CI 1.2–12.7) whereas the OR was 0.86 (95 % CI 0.65–1.13) for those without prior infection.
There was a significant interaction between the GNβ3 polymorphism and infection in the development of IBS, suggesting that its etiology is the result of a combination of specific genetic and environmental risk factors.
KeywordsIrritable bowel syndrome Genes Genetics Infection
This study was supported in part by research grants from the National Institutes of Health (K23 DK66271), the American Gastroenterological Association, and Solvay Pharmaceuticals.
Conflict of interest
- 20.Camilleri M, Busciglio I, Carlson P, et al. Candidate adrenergic, GMβ3, and serotonergic polymorphisms, endophenotype, pharmacogenetics of clonidine in irritable bowel syndrome and health. Gastroenterology 2008;134:A-682.Google Scholar
- 23.Thompson WG, Creed FH, Drossman DA, Heaton KW, Mazzacca G. Functional bowel disease and functional abdominal pain. Gastrenterol Int. 1992;5:75–91.Google Scholar
- 24.Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Muller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut 1999;45:II43–II47.Google Scholar
- 28.Beck AT, Steer RA. Manual for the Beck Anxiety Inventory. San Antonio: Psychological Corporation; 1990.Google Scholar
- 34.Locke GR, 3rd, Zinsmeister AR, Fett SL, Melton LJ, 3rd, Talley NJ. Overlap of gastrointestinal symptom complexes in a U.S. community. Neurogastroenterol Motil. 2005;17:29–34.Google Scholar