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

摘要

Single-nucleotide polymorphisms (SNPs) of the beta-adrenergic receptor (betaADR) subtypes are related to hypertension and obesity. This hospital-based cohort study with hypertensive patients evaluated five pADR SNPs in association with cardiovascular events. The cohort included 357 hypertensive patients (male=181; mean age=61.5+- 11.8 years) seen between January 1998 and June 2004. The SNPs (Ser49Gly and Arg389Gly for beta_1ADR; Glyl6Arg and Glu27Gln for beta_2ADR; Trp64Arg for beta_3ADR) 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/Gly=243:104:10; Arg/Arg:Arg/Gly:Gly/Gly=256:95:6; Gly/Gly:Gly/Arg:Arg/ Arg=71:201:85; Gln/Gln:Glu/Gln=308:49; and Trp/Trp:Trp/Arg:Arg/Arg=265:89:3. A total of 17 stroke and 15 coronary artery disease cases were recorded. By Kaplan-Meier analysis, the Ser/Ser SNP in Ser49Gly (P=0.0398), the Glu/GIn SNP in Glu27Gln (P=0.0390) and the Trp/Trp SNP in Trp64Arg (P=0.0132) 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 (P=0.0321) and age (P=0.0186) 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 beta_1, Glu/GIn in Glu27Gln of beta_2 and Trp/Trp in Trp64Arg of beta_3 (P=0.0209). These three SNPs, especially the Trp64Arg SNP of beta_3ADR, might be risk factors for CVD in hypertensive patients.