Β-Adrenergic receptor gene polymorphism is a genetic risk factor for cardiovascular disease: A cohort study with hypertensive patients

Abstract

Single-nucleotide polymorphisms (SNPs) of the Β-adrenergic receptor (ΒADR) subtypes are related to hypertension and obesity. This hospital-based cohort study with hypertensive patients evaluated five ΒADR SNPs in association with cardiovascular events. The cohort included 357 hypertensive patients (male181; mean age61.511.8 years) seen between January 1998 and June 2004. The SNPs (Ser49Gly and Arg389Gly for Β 1 ADR; Gly16Arg and Glu27Gln for Β 2 ADR; Trp64Arg for Β 3 ADR) were identified by PCR. We used Kaplan-Meier curves to assess the prognostic effect of these SNPs on cardiovascular disease (CVD). The SNP frequencies were Ser/Ser:Ser/Gly:Gly/ Gly243:104:10; Arg/Arg:Arg/Gly:Gly/Gly256:95:6; Gly/Gly:Gly/Arg:Arg/Arg71:201: 85; Gln/Gln:Glu/Gln308:49; and Trp/Trp:Trp/Arg:Arg/Arg265:89:3. A total of 17 stroke and 15 coronary artery disease cases were recorded. By Kaplan-Meier analysis, the Ser/Ser SNP in Ser49Gly (P0.0398), the Glu/Gln SNP in Glu27Gln (P0.0390) and the Trp/Trp SNP in Trp64Arg (P0.0132) were associated with lower event-free CVD survival (log-rank, Mantel-Cox model). A Cox proportional hazards model revealed that only the Trp/Trp SNP (P0.0321) and age (P0.0186) were independently related to lower event-free survival for CVD, adjusted for gender, diabetes, dyslipidemia, blood pressure, body mass index, medication and hypertensive complications. Combination Kaplan-Meier analysis of these three positive SNPs indicated a higher frequency of CVD among patients with the combination of Ser/Ser in Ser49Gly of Β 1, Glu/Gln in Glu27Gln of Β 2 and Trp/Trp in Trp64Arg of Β 3 (P0.0209). These three SNPs, especially the Trp64Arg SNP of Β 3 ADR, might be risk factors for CVD in hypertensive patients. © 2011 The Japanese Society of Hypertension All rights reserved.