Association between GNB3 c.825C > T polymorphism and the risk of overweight and obesity: A meta-analysis.
BACKGROUND
The association between G protein β-polypeptide 3 gene (GNB3) c.825C > T polymorphism (rs5443) and the risk of overweight/obesity has been investigated in many published studies, but the results were conflicting and inconclusive. A meta-analysis was performed to make a more accurate assessment of the relationship.


METHODS
The PubMed, ProQuest Health & Medical Complete, Web of Science, Chinese Biomedical Medical databases (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched to identify eligible literatures. Pooled odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were used to assess the strength of association between GNB3 c.825C > T polymorphism and overweight/obesity.


RESULTS
Eleven articles including 15 case-control studies with a total of 10,396 subjects (3171 cases of overweight/obesity and 7225 controls) were enrolled in the meta-analysis. The GNB3 c.825C > T was significantly associated with overweight/obesity under a recessive model (OR = 1.22, 95% CI: 1.04-1.44, P = 0.015). Moreover, the GNB3 825T allele was obviously associated with overweight alone in all inheritable models (P < 0.05) except in a recessive model (P = 0.084). In the stratification analysis by potential confounding variables, a significant association was observed between GNB3 c.825C > T polymorphism and overweight/obesity risk in males under an allelic model (P = 0.008), a homozygous model (P = 0.014), a recessive model (P = 0.005), and a dominant model (P = 0.049). And the results also showed that GNB3 c.825C > T polymorphism was significantly associated with overweight/obesity in subgroups of mean age less than 30 years, consistent with HWE, and high-quality studies (P = 0.027, P = 0.043, P = 0.040, respectively) under a recessive model, but not in other subgroups. Meta-regression also revealed that P value of HWE, publication year, and the quality scores of studies were the sources of heterogeneity in a recessive model and an allelic model. "Leave one out" sensitivity analyses indicated that the association was more significant after excluding some studies. The funnel plot and Egger's linear regression test and Begg's test revealed no apparent publication bias.


CONCLUSIONS
This meta-analysis suggests that the presence of TT homozygote might be one of the genetic factors susceptible to overweight/obesity and that males or aged under 30 years increase the genetic susceptibility.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China; School of Pharmaceutical Science, Central South University, Changsha 410013, Hunan, PR China.
Hui-Lan
HL
Li
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China.
Yan-Jiao
YJ
Zhang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China.
Xiao-Ping
XP
Chen
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China.
Jian-Quan
JQ
Luo
School of Public Health, Central South University, Changsha 410078, Hunan, PR China.
Si-Yun
SY
Liu
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
Zan-Lin
ZL
Zhang
BMI, body mass index; CBM, Chinese Biomedical Medical databases; CIs, confidence intervals; CNKI, Chinese National Knowledge Infrastructure; G protein β-polypeptide 3; GNB3, G protein β-polypeptide 3 gene; HB, hospital based; HWE, Hardy–Weinberg equilibrium; MOOSE, guidelines from meta-analysis of observational studies in epidemiology; Meta-analysis; NOS, the Newcastle–Ottawa Quality Assessment Scale; ORs, pooled odds ratios; Obesity; Overweight; PB, population based; PCR–RFLP, polymerase chain reaction–restriction fragment length polymorphism; Polymorphism; WHO, World Health Organization