Haplotype analysis of CYP11B2

Polymorphisms affecting the synthesis of aldosterone or its regulation may have effects on blood pressure. For example, an autosomal dominant form of human hypertension, glucocorticoid suppressible hyperaldosteronism, is caused by recombination between the genes for aldosterone synthase (CYP11B2) and steroid 11 beta-hydroxylase (CYP11B1), creating a chimeric gene in which the CYP11B1 promoter and CYP11B2-specific coding sequences are juxtaposed. Thus, aldosterone synthesis is improperly regulated. We have begun an analysis of the human CYP11B2 and CYP11B1 genes to see if frequent polymorphisms exist and if they are correlated with differences in blood pressure. We have found frequent polymorphisms in CYP11B2. One in the promoter influences binding of the transcriptional regulatory protein, SF-1. Another is a gene conversion in intron 2 so that most of the intron has a sequence corresponding to CYP11B1. These polymorphisms are in linkage disequilibrium, defining 3 haplotypes. Blacks and whites differ significantly (p < 0.001) in the frequency with which these haplotypes occur. Further studies are required to determine if the observed differences between blacks and whites in blood pressure and in aldosterone levels can be explained in part by these allelic differences in CYP11B2 or by other polymorphisms in linkage disequilibrium on these haplotypes.