Endocrine Abstracts

Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes are highly homologous in their coding regions (95%), lie in tandem approximately 40kb apart in human chromosome 8, and may have arisen from gene duplication. The pattern of linkage disequilibrium (LD) of this region in a population is determined not only by the distribution of recombination events but also by demographic factors determining the amount of random genetic drift. There is suggestive evidence that LD of the aldosterone synthase gene differs in populations of white and black ancestry, with the former associated with much tighter LD across the region. LD patterns of essential hypertensive patients with different ancestries have not been determined in the locus comprising both genes and this would be important in dissecting the role of aldosterone in essential hypertension.

Polymorphisms and LD patterns of the CYP11B1/B2 locus were studied in two independent populations in 248 Caucasian families (1428 individuals) and 45 Afro-Caribbean families (251 individuals) ascertained via a hypertensive proband. Genetic marker selection in both studies was based on SNPs likely to be functional as well as informative according to the LD in the region. Five polymorphisms were typed in both populations; three of these had different allele frequencies between the populations. We show differences in LD as demonstrated by differences in SNP coverage (Europeans=87%; Afro-Caribbeans=53%) and allele frequencies (Table) across the CYP11B1/B2 region. The high degree of LD among Europeans makes identification of true causal variants difficult. Studies which make use of the differences in LD structure between European and African ancestry populations have the potential to enable identification of causal variants for blood pressure regulation and hypertension.