One hundred thirty-six unrelated hypertensives and eighty-one unrelated normotensives of African Caribbean origin were identified from primary care on the island of St. Vincent (demographic data are summarised in table 3.1). Genomic DNA from these subjects was analysed for the presence of the Gly16 and Arg16 as well as the Glu27 and Gln27 alleles by using an allele-specific PCR method (for protocol details see section 3.3.3). Genotyping of the β2 adrenergic receptor variant was cross-checked by an individual who was unaware of the subject’s phenotype, and all genotypes were repeated twice to confirm assignment.
The distribution of β2 adrenoceptor alleles for the Arg/Gly16 alleles did not confirm to Hardy-Weinberg equilibrium in this study. However, the careful ascertainment of hypertensive and control subjects from the same population, coupled with previous published observations of Hardy-Weinberg equilibrium in the same population with several diallelic markers at other loci, makes selection bias in our cohorts highly unlikely [45, 165]. In addition, all genotypes were repeated twice for conformation, and these results were cross-checked in 18 individuals by direct sequencing, which confirmed our data in all cases and minimised the risk of laboratory error during genotyping.
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There was marked disequilibrium in the distribution of genotypes (Gly16, Gly16Arg, and Arg16) between normotensives and hypertensives (χ2= 14.6, P=.0007, 2 df ), with the number of Gly16 homozygotes markedly increased in the hypertensive subjects (Table 3.3). The frequency of the Gly16 allele in the hypertensive patients was 0.85 and in the normotensive controls 0.64 (χ2= 18.9, P=.000014, 1 df ). The relative risk of hypertension associated with alleles of the β2 adrenergic receptor gene was increased, with a corrected odds ratio of 2.74 (95% confidence limits, 1.72 to 4.36).
The distribution of β2 adrenoceptor alleles for the Gln/Glu27 alleles did confirm to Hardy-Weinberg equilibrium. The allelic variants at position 27 did not differ significantly between the hypertensive and normotensive groups (the frequency of the Gln27 allele was 0.84 in hypertensive patients as well as in normotensive controls) and were not in linkage disequilibrium to the position 16 alleles (Table 3.4).
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© 2001 Alexander Binder