Synopsis and data synthesis of genetic association studies in hypertension for the adrenergic receptor family genes: the CUMAGAS-HYPERT database.

BACKGROUND The adrenergic receptor (adrenoceptor) family genes have been extensively studied as candidate genes in hypertension but the results of individual genetic association studies (GAS) are controversial and inconclusive. To clarify these data, a systematic assessment of GAS for adrenoceptor family genes in hypertension was conducted. METHODS Data from 163 GAS involving 7 genes and 37 distinct genetic variants were analyzed and cataloged in CUMAGAS-HYPERT (Cumulative Meta-analysis of Genetic Association Studies-HYPERTension; a web-based information system, which allows the retrieval and synthesis of data from GAS in hypertension, available at http://biomath.med.uth.gr). Data from genome-wide association studies involving the adrenoceptor family genes were also systematically searched. RESULTS Individual GAS reported inconsistent associations and had limited power to detect modest genetic effects, with only 1.2% having power >80%. Thirteen variants were investigated by three or more studies and their results were subject to meta-analysis. In the main meta-analyses, significant results were shown for five variants (ADRB1 p.Arg389Gly, ADRB1 p.Ser49Gly, ADRB2 g.9368308A>G, ADRB3 p.Trp64Arg, and ADRA1A p.Cys347Arg) under the allelic contrast and/or the dominant model. Subgroup analyses by ethnicity and gender detected significant associations for three variants (ADRB1 p.Arg389Gly in east Asians, ADRB2 p.Gln27Glu in whites, and ADRB3 p.Trp64Arg in whites and in males). Heterogeneity ranged from none to high. No significant associations were recorded from genome-wide studies. CONCLUSIONS There is evidence to implicate adrenoceptor genes in hypertension, although future studies designed to investigate epistatic and gene-environment interactions would allow more solid conclusions to be drawn about the role of these genes in hypertension.