title: The role of 5-HTT LPR and GNβ3 825C>T polymorphisms and gene-environment interactions in irritable bowel syndrome (IBS).
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. saito.yuri@mayo.edu
authors.forename: Yuri A
authors.initials: YA
authors.lastname: Saito
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Larson
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Atkinson
authors.forename: Euijung
authors.initials: E
authors.lastname: Ryu
authors.forename: Ann E
authors.initials: AE
authors.lastname: Almazar
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Talley
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D044127:Epigenesis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological; D055815:Young Adult
chemical_list: C454420:G-protein beta3 subunit; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D020962:Heterotrimeric GTP-Binding Proteins