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The Role of 5-HTT LPR and GNβ3 825C>T Polymorphisms and Gene–Environment Interactions in Irritable Bowel Syndrome (IBS)

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Abstract

Background

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.

Aims

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

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

None.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Yuri A. Saito, Ann E. Almazar & Nicholas J. Talley

  2. Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Joseph J. Larson, Elizabeth J. Atkinson & Euijung Ryu

  3. Division of Epidemiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Gloria M. Petersen

  4. Faculty of Health, University of Newcastle, Callaghan, NSW, 2308, Australia

    Nicholas J. Talley

Authors
  1. Yuri A. Saito
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Correspondence to Yuri A. Saito.

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Saito, Y.A., Larson, J.J., Atkinson, E.J. et al. The Role of 5-HTT LPR and GNβ3 825C>T Polymorphisms and Gene–Environment Interactions in Irritable Bowel Syndrome (IBS). Dig Dis Sci 57, 2650–2657 (2012). https://doi.org/10.1007/s10620-012-2319-9

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  • DOI: https://doi.org/10.1007/s10620-012-2319-9

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