Endocrine Abstracts (2002) 3 P159

Single nucleotide polymorphisms of the beta2-adrenergic receptor (ADRB2) gene and hypertension

NJR Brain1, M Tomaszewski2, B Lacka2, FJ Charchar1, W Wang3, S Padhmanaban1, NH Anderson1, E Zukowska-Szczechowska2, W Grzeszczak2 & AF Dominiczak1

1BHF Blood Pressure Group, Medicine & Therapeutics, University of Glasgow, UK; 2Internal Medicine, Diabetology & Nephrology, Silesian School of Medicine, Zabrze, Poland; 3Wellcome Trust Centre for Molecular Mechanisms in Disease, University of Cambridge, UK.

Objective: Three nonsynonomous SNPs, Arg16Gly, Gln27Glu and Thr164Ile, in the coding region of the ADRB2 gene affect either receptor affinity or trafficking. Their distribution has been shown to differ significantly in hypertension. We investigated the association of these loci with hypertension in the Silesian Hypertension Study.

Methods: Following local ethics approval, 274 unrelated Polish subjects consisting of 146 hypertensives and 128 normotensives for whom blood pressure and other phenotypic and clinical data were available, were genotyped at the three polymorphic loci. Genotypes and allele frequencies were compared for hypertensives and normotensives by chi^2 test. Association of each locus with hypertension was assessed using binary logistic regression.

Results: There was no significant difference between hypertensives and normotensives for either the genotype distributions of Arg16Gly, Gln27Glu and Thr164Ile (chi^2=5.23, p=0.0731; chi^2=0.421, p=0.421; chi^2=0.440, p=0.507) or the allele frequencies (chi^2=0.5312, p=0.47; chi^2=0.26, p=0.61; chi^2=0.44, p=0.51). The OR of hypertension adjusted for age, sex and BMI in those with no mutant alleles versus those with either one or two were 0.85 (95% CI, 0.3 to 2.2, p=0.74) and 1.46 (95% CI, 0.5 to 4.2, p=0.49) for Arg16Gly; 1.33 (95% CI, 0.6 to 3.1, p=0.5) and 1.54 (95% CI, 0.5 to 4.4, p=0.43) for Gln27Glu and 0.7 (95% CI, 0.1 to 4.9, p=0.72) for Thr164Ile. No Thr164Ile mutant homozygotes existed in the cohort.

Conclusions: No significant associations were found between any of the three loci and hypertension and they were not significant predictors of hypertension. This case-control study does not support a role for these ADRB2 mutations in the pathogenesis of hypertension in this population.

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