title: 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 (male = 181; mean age = 61.5 ± 11.8 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/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/Gln 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 β(1), Glu/Gln in Glu27Gln of β(2) and Trp/Trp in Trp64Arg of β(3) (P = 0.0209). These three SNPs, especially the Trp64Arg SNP of β(3)ADR, might be risk factors for CVD in hypertensive patients.
authors.affiliation: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohishi
authors.forename: Ming
authors.initials: M
authors.lastname: Yuan
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tatara
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takeya
authors.forename: Miyuki
authors.initials: M
authors.lastname: Onishi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics*; D003920:Diabetes Mellitus / Q000453:epidemiology; D050171:Dyslipidemias / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*
chemical_list: D011943:Receptors, Adrenergic, beta