G Protein beta3 Subunit Polymorphism and Long-Term Prognosis of Functional Dyspepsia

BACKGROUND/AIMS: A link between G protein beta3 (GNB3) polymorphism and functional dyspepsia (FD) has been suggested. The aim of this study was to determine the role of GNB3 polymorphism in the long-term prognosis of FD in Koreans. METHODS: FD patients and normal healthy controls were recruited from patients who visited our center between December 2006 and June 2007. All of the subjects completed Rome III questionnaires before undergoing upper gastrointestinal endoscopy and colonoscopy. Genomic DNA was extracted for GNB3 genotyping. After 5 years, the subjects were reevaluated using the same questionnaires. RESULTS: GNB3 825T carrier status was significantly related to FD in Koreans (p=0.04). After 5 years, 61.0% of the initial FD patients and 12.2% of the initial normal subjects were diagnosed with FD (odds ratio [OR], 11.7; 95% confidence interval [CI], 4.3 to 31.1; p<0.001). Regardless of the GNB3 genotype (p=0.798), female sex was strongly correlated with FD after 5 years (OR, 3.3; 95% CI, 1.2 to 9.1; p=0.017). CONCLUSIONS: The T allele of GNB3 is linked to FD in Koreans but does not predict long-term prognosis. Female sex is related to a higher prevalence of FD after 5 years.

Association between polymorphism of the G-protein β3 subunit C825T and essential hypertension: an updated meta-analysis involving 36,802 subjects

Purpose: The G-protein β3-subunit gene C825T polymorphism (GNB3-C825T) has been reported to be associated with essential hypertension (EH), but results from previous studies are conflicting. The present study aimed at investigating the association between this polymorphism and risk of EH using a meta-analysis on the published studies. Materials and Methods: PubMed, Embase, CBM (China Biological Medicine Database), Wanfang and VIP databases were searched to identify eligible studies published in English and Chinese before March 2013. Data were extracted using standardized methods. The association was assessed by the odds ratio (OR) with 95% confidence intervals (CI). Begg's test was used to measure publication bias. Results: A total of 40 case-control studies containing 16,518 EH patients and 20,284 controls were involved in this meta-analysis. Overall, a significant association was found between GNB3 C825T polymorphism and risk of EH when all studies were pooled with a random-effects model for T versus C (OR=1.09, 95% CI: 1.04-1.19). In the subgroup analysis, the same association was found in overall Caucasian (T versus C, OR=1.16, 95% CI 1.08-1.24) and Chinese populations (TT versus CC, OR=1.23, 95% CI 1.06-1.57). No associations were detected between GNB3-C825T and the risk of EH overall in Asian and Japanese people. Conclusions: Meta-analysis results suggest that the GNB3-C825T polymorphism is associated with risk of EH in the overall population, the Caucasians and the Chinese. The effect of the variants on the expression levels and the possible functional role of the variants in EH should be addressed in further studies.

Adaptation of cAMP signaling system in SH-SY5Y neuroblastoma cells following expression of a constitutively active stimulatory G protein alpha, Q227L Gsalpha

Heterotrimeric GTP-binding proteins (G protein) are known to participate in the transduction of signals from ligand activated receptors to effector molecules to elicit cellular responses. Sustained activation of cAMP-G protein signaling system by agonist results in desensitization of the pathway at receptor levels, however it is not clear whether such receptor responses induce other changes in post-receptor signaling path that are associated with maintenance of AMP levels, i.e. cAMP-forming adenylate cyclase (AC), cAMP-degrading cyclic nucleotide phosphodiesterase (PDE) and cAMP-dependent protein kinase (PKA). Experiments were performed to determine the expression of AC, PDE, and PKA isoforms in SH-SY5Y neuroblastoma cells, in which cAMP system was activated by expressing a constitutively activated mutant of stimulatory G protein (Q227L Gsalpha). Expression of ACI mRNA was increased, but levels of ACVIII and ACIX mRNA were decreased. All of the 4 expressed isoforms of PDE (PDE1C, PDE2, PDE 4A, and PDE4B) were increased in mRNA expression; the levels of PKA RIalpha, RIbeta, and RIIbeta were increased moderately, however, those of RIIalpha and Calpha were increased remarkably. The activities of AC, PDE and PKA were also increased in the SH-SY5Y cells expressing Q227L Gsalpha. The similar changes in expression and activity of AC, PDE and PKA were observed in the SH-SY5Y cells treated with dbcAMP for 6 days. Consequently, it is concluded that the cAMP system adapts at the post-receptor level to a sustained activation of the system by differential expression of the isoforms of AC, PDE, and PKA in SH-SY5Y neuroblastoma. We also showed that an increase in cellular cAMP concentration might mediate the observed changes in the cAMP system.