Combination of polymorphisms in the β2-adrenergic receptor and nitric oxide synthase 3 genes increases the risk for hypertension

Objective: Hypertension is a major risk factor for cardiovascular disease. Polymorphism in the β2-adrenergic receptor (ADRB2) and nitric oxide synthase 3 (NOS3) genes is associated with clinical cardiovascular phenotypes. The Arg16Gly and Glu298Asp polymorphisms of ADRB2 and NOS3 genes, respectively, have been reported to be associated with hypertension. We hypothesized that a combination of these two polymorphisms increases the risk for hypertension. Hence, we examined the effect of this combination of single-nucleotide polymorphisms on the risk for hypertension. Methods: Our cross-sectional study comprised 402 middle-aged and elderly human participants. We determined the genotypes of Arg16Gly and Glu298Asp single-nucleotide polymorphisms in ADRB2 and NOS3, respectively, by TaqMan PCR method; we also measured the resting blood pressure. Results: The odds ratio for the presence of hypertension in individuals having the Gly/Gly genotype of ADRB2 compared with those having the other genotypes (Arg/Arg and Arg/Gly) was 2.87. With regard to the Glu298Asp polymorphism in NOS3, the odds ratio for the presence of hypertension in individuals having the Glu/Glu genotype of NOS3 when compared with those having the other genotypes (Asp/Asp and Asp/Glu) was 2.79. Interestingly, the odds ratio was 7.64 for individuals having a combination of the Gly/Gly genotype of ADRB2 and Glu/Glu genotype of NOS3 when compared with those having a combination of Arg/Arg and Arg/Gly genotypes of ADRB2 and Asp/Asp and Asp/Glu genotypes of NOS3. Conclusion: We revealed that a combination of the Arg16Gly and Glu298Asp polymorphisms in ADRB2 and NOS3, respectively, remarkably increased the risk for hypertension in middle-aged and elderly humans.