Multivariate meta-analysis of the association of G-protein beta 3 gene (GNB3) haplotypes with cardiovascular phenotypes

Mol Biol Rep. 2014 May;41(5):3113-25. doi: 10.1007/s11033-014-3171-0. Epub 2014 Jan 30.


The objective of the present study was to review previous investigations on the association of haplotypes in the G-protein β3 subunit (GNB3) gene with representative cardiovascular risk factors/phenotypes: hypertension, overweight, and variation in the systolic and diastolic blood pressures (SBP and DBP, respectively) and as well as body mass index (BMI). A comprehensive literature search was undertaken in Pubmed, Web of Science, EMBASE, Biological Abstracts, LILACS and Google Scholar to identify potentially relevant articles published up to April 2011. Six genetic association studies encompassing 16,068 participants were identified. Individual participant data were obtained for all studies. The three most investigated GNB3 polymorphisms (G-350A, C825T and C1429T) were considered. Expectation-maximization and generalized linear models were employed to estimate haplotypic effects from data with uncertain phase while adjusting for covariates. Study-specific results were combined through a random-effects multivariate meta-analysis. After carefully adjustments for relevant confounding factors, our analysis failed to support a role for GNB3 haplotypes in any of the investigated phenotypes. Sensitivity analyses excluding studies violating Hardy-Weinberg expectations, considering gender-specific effects or more extreme phenotypes (e.g. obesity only) as well as a fixed-effects "pooled" analysis also did not disclose a significant influence of GNB3 haplotypes on cardiovascular phenotypes. We conclude that the previous cumulative evidence does not support the proposal that haplotypes formed by common GNB3 polymorphisms might contribute either to the development of hypertension and obesity, or to the variation in the SBP, DBP and BMI.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Alleles
  • Blood Pressure / genetics*
  • Exons
  • Genetic Association Studies*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Haplotypes*
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Humans
  • Hypertension / genetics*
  • Odds Ratio
  • Overweight / genetics*
  • Patient Outcome Assessment
  • Promoter Regions, Genetic


  • 3' Untranslated Regions
  • G-protein beta3 subunit
  • Genetic Markers
  • Heterotrimeric GTP-Binding Proteins