The G-Protein β3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia

Abstract

BackgroundAlthough familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein β3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up.MethodsSubjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables.ResultsThe GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91).ConclusionThe homozygous GNB3 825T allele influences the susceptibility to EPS-like dyspepsia.

Functional dyspepsia

“…Polymorphisms in the gene G protein subunit β3 (GNB3) affect a large number of functions, including adrenergic, serotonergic and immune functions 108 , all of which are potentially important for the manifestation of functional dyspepsia. After an initial study that revealed an association between a specific GNB3 genotype and functional dyspepsia on the basis of population-based patient cohorts 109 , subsequent studies have confirmed this link [110][111][112] . Interestingly, some studies found this correlation only in patients without H. pylori infection 112 or with specific symptom manifestations, such as EPS 110 .…”

“…After an initial study that revealed an association between a specific GNB3 genotype and functional dyspepsia on the basis of population-based patient cohorts 109 , subsequent studies have confirmed this link [110][111][112] . Interestingly, some studies found this correlation only in patients without H. pylori infection 112 or with specific symptom manifestations, such as EPS 110 . This observation might suggest a specific interaction between H. pylori infection and GNB3.…”

The development of functional gastrointestinal diseases: Genetic aspects

“…ма C825T гена GNB3 установлена с высоким риском развития как постпрандиального дистресс-синдрома [5], так и эпигастрально-го болевого синдрома (ЭБС) [6]. В другом исследовании выявлен высокий риск развития ФД у носителей гена TRPV1 G315C [7].…”

“…Кроме того, не удалось выявить связей между генетически-ми особенностями полиморфизма гена эндоканнабиноидного метаболизма (C385A) у пациентов с сочетанием нарушения акко-модации фундального отдела желудка с нарушением опорожне-ния желудка у небольшой группы больных ФД [6].…”

Features of the autonomic nervous system in children with gastroesophageal reflux disease and different genotypes of C825t locus of Gnb3 gene

“…За результатами інших досліджень між GNB3 C825T ге-нотипом і симптомами ГЕРХ зв'язку не виявлено [23].…”