Published Online
on August 4, 2003

A more recent version of this article appeared on October 1, 2003

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Submitted on May 12, 2003
Revised on June 9, 2003

2 Adrenoceptor Functional Gene Variants, Obesity, and Blood Pressure Level Interactions in the General Population

Alexandre C. Pereira; Marcilene S. Floriano; Glória F.A. Mota; Roberto S. Cunha; Fernando L. Herkenhoff; José G. Mill; and José E. Krieger^*

From the Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), São Paulo University Medical School (A.C.P., M.S.F., G.F.A.M., J.E.K.), São Paulo, Brazil; and the Department of Physiology, Espirito Santo Federal University (R.S.C., F.L.H., J.G.M.), Vitoria, Brazil.

^* To whom correspondence should be addressed. E-mail: krieger{at}incor.usp.br.

Abstract--We investigated the association of 2 adrenoceptor functional gene variants (Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms), obesity phenotypes, and blood pressure levels in a large, ethnically mixed urban population. The individuals (n=1576) were randomly selected for a cross-sectional study of cardiovascular risk factors in Vitória, Brazil. Statistically significant associations among systolic blood pressure and the Arg16Gly and Thr164Ile variants were identified in univariate analysis. The Gly16/Gly16 genotype was still associated with systolic blood pressure (SBP) in multivariate analysis adjusting for age, gender, ethnicity, total cholesterol, diabetes, and body mass index (BMI) (P=0.01). The Arg16 allele was the only genotypic variable associated with BMI, and, in a dominant model, it remained associated with an increased BMI even after adjustment for age, gender, ethnicity, triglycerides, HDL cholesterol, LDL cholesterol, diabetes, and hypertension status (P=0.02). Although the different polymorphisms did not interact in the determination of SBP, a significant interaction with BMI (P=0.02), not through linkage disequilibrium, was identified between the Gln27Glu and the Thr164Ile variants. Furthermore, a significant interaction among the Arg16Gly polymorphism and BMI (P=0.036) and waist-hip ratio (P=0.003) in determining SBP was disclosed by ANOVA factorial modeling, with SBP used as the dependent variable. An interaction between the Thr164Ile polymorphism and waist-hip ratio was also identified (P=0.018). Finally, multiple logistic regression models showed a 1.48-fold increase in the risk of hypertension in individuals harboring the Gly16/Gly16 genotype and a 1.31-fold (P=0.01) and a 1.49-fold (P=0.003) increased risk of obesity in individuals harboring the Gln27/Gln27 genotype or the presence of the Arg16 allele, respectively. Taken together, these data provide evidence for a strong but complex relation between -adrenoceptor gene variants, hypertension, and obesity.

Key words: receptors, adrenergic beta • hypertension, obesity • genetics • polymorphism

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