An exploratory study of the association of adrenergic and serotonergic genotype and gastrointestinal motor functions.

Adrenergic and serotonergic mechanisms alter human gut motor functions. Genotype variation influences phenotype. Our aim was to test the hypothesis that variation in genes that control these functions is associated with gastrointestinal (GI) motor functions in humans with functional GI disorders (FGID). A database of 251 people was assembled by combining genotype data with measurements of gut transit and gastric volumes. Genetic variations evaluated were: alpha(2A) adrenergic (C-1291G), alpha(2C) (Del 332-325), 5-HT transporter (SLC6A4) and GNbeta3 (C825T). We sought associations between motor function or disease groups and genotypes, adjusting for age, gender and body mass index. Among 251 participants, 82 were healthy, 20 with irritable bowel syndrome (IBS) with mixed bowel habit, 49 with constipation-predominant IBS, 67 with diarrhoea-predominant IBS and 33 with functional dyspepsia. For all candidate genes, there was no significant association between motor function and wildtype vs non-wildtype gene status. There were significant interactions between genotype and motility phenotype, specifically GNbeta3 and alpha(2A) and gastric emptying at 4 h. Borderline associations were noted for SCL6A4 and alpha(2A) and postprandial gastric volume, and for alpha(2C) and gastric emptying at 2 h. We conclude that genotype variation may affect gastric motor functions in different FGID phenotypes. However, these candidate genes account for only a limited amount of the variance in gastric function of patients with FGID.