Is There an Association Between GNβ3-C825T Genotype and Lower Functional Gastrointestinal Disorders?

Background & Aims: GNβ3 influences G-protein translation of a majority of ligand-receptor activations. It has been reported that functional dyspepsia (FD) is associated with homozygous genotypes of the C825T polymorphism in the GNβ3 gene. It is unknown whether the GNβ3 genotype is associated with lower functional gastrointestinal disorders (FGID). We aimed to compare the prevalence of the different GNβ3-C825T genotypes in patients with lower FGID and healthy controls and to test the associations of these genetic variations with subgroups of irritable bowel syndrome (IBS), functional abdominal pain (FAP), lower FGID-FD overlap, and high somatic symptom scores. Methods: GNβ3-C825T polymorphism was analyzed in DNA from blood samples of 233 patients with lower FGID and 152 healthy controls. A validated bowel questionnaire characterized the FGID phenotype: 82 with IBS constipation, 94 with IBS diarrhea, 38 with IBS alternating bowel function, and 19 with FAP. There were 159 patients with lower FGID and overlap FD using Rome II criteria. Regression analyses assessed associations of the GNβ3 genotypes with lower FGID as a group, and subgroups of FGID and somatic symptom scores. Results: GNβ3-C825T genotype distributions were similar between healthy controls (50.7% CC, 40.8% TC) and patients with lower FGID (8.6% TT, 51.5% CC, 40.8% TC, and 7.7% TT). There were no significant associations of GNβ3-C825T polymorphism with lower FGID overall or with the separate symptom subgroups including IBS, FAP, lower FGID-FD overlap, or high somatic symptom scores. Conclusions: In contrast to the reported association with FD, GNβ3-C825T polymorphism is not associated significantly with lower FGID, with different IBS or FAP phenotypes, or lower FGID-FD overlap.