HAPLOTYPE ANALYSIS OF CYP11B2

Polymorphisms affecting the synthesis of aldosterone or its regulation may have effects on blood pressure. For example, an autosomal dominan t form of human hypertension, glucocorticoid suppressible hyperaldoste ronism, is caused by recombination between the genes for aldosterone s ynthase (CYP11B2) and steroid 11 beta-hydroxylase (CYP11B1), creating a chimeric gene in which the CYP11B1 promoter and CYP11B2-specific cod ing sequences are juxtaposed. Thus, aldosterone synthesis is improperl y regulated. We have begun an analysis of the human CYP11B2 and CYP11B 1 genes to see if frequent polymorphisms exist and if they are correla ted with differences in blood pressure. We have found frequent polymor phisms in CYP11B2. One in the promoter influences binding of the trans criptional regulatory protein, SF-1. Another is a gene conversion in i ntron 2 so that most of the intron has a sequence corresponding to CYP 11B1. These polymorphisms are in linkage disequilibrium, defining 3 ha plotypes. Blacks and whites differ significantly (p < 0.001) in the fr equency with which these haplotypes occur. Further studies are require d to determine if the observed differences between blacks and whites i n blood pressure and in aldosterone levels can be explained in part by these allelic differences in CYP11B2 or by other polymorphisms in lin kage disequilibrium on these haplotypes.