G-protein β3 subunit 825CC genotype is associated with postprandial distress syndrome with impaired gastric emptying and with the feeling of hunger in Japanese


Address for Correspondence
Seiji Futagami, Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
Tel:+81 3 3822 2131; fax: +81 3 5685 1793; e-mail: seiji.futagami@gmail.com


Background  G-protein dysfunction related alteration of intracellular signal transduction might be linked to various abnormalities of functional gastrointestinal (GI) disorders. Serotonin (5-hydroxytryptamine; 5-HT) as well as G-protein is also key signaling molecule sensorimotor functions in the GI tract. Thus, this study aims to evaluate the correlation between gastric emptying and GNβ3 and 5-HTs polymorphisms in functional dyspepsia (FD) as defined by Rome III classification.

Methods  Seventy-four patients presenting with typical symptoms of FD (epigastric pain syndrome: EPS, = 24; postprandial distress syndrome: PDS, = 51) and sixty-four healthy volunteers were enrolled. Gastric motility was evaluated with the Tmax value using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and SRQ-D scores to determine depression status. GNβ3-C825T, 5-HT1A-C1019G, 5-HT2A-G1438A, 5-HT3A-C42T, and 5-HT4A-G353 + 6A polymorphisms were analyzed in DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction.

Key Results  There was a significant relationship (= 0.045) between GNβ3 825CC genotype and PDS patients without gastro-esophageal reflux symptoms with impaired gastric emptying. In Japanese, GNβ3 825CC genotype in FD patients was significantly associated (= 0.0485) with the feeling of hunger compared with GNβ3 825CT and TT genotypes.

Conclusions & Inferences  Our results suggest that the GNβ3 825CC genotype is significantly associated with PDS patients without gastro-esophageal reflux with impairments of gastric emptying and also with the feeling of hunger in patients with FD. Further studies are needed to clarify whether the GNβ3 825CC genotype is linked to disturbances of gastric emptying via altered signal transduction responses.