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Journal of Clinical Endocrinology & Metabolism, Vol 81, 3254-3256, Copyright © 1996 by Endocrine Society

ARTICLES

The human genome contains only two CYP11B (P450c11) genes

G Zhang and WL Miller
Department of Pediatrics, University of California, San Francisco 94143- 0978, USA.

The biosynthesis of glucocorticoids and mineralocorticoids requires isozymes of P450c11. Two human isozymes are known: P450c11 beta, encoded by the CYP11B1 gene, has 11 beta-hydroxylase activity; P450c11AS, encoded by the CYP11B2 gene, has 11 beta-hydroxylase, 18- hydroxylase, and aldosterone synthase activities. Recent data show that the rat genome has four CYP11B genes, three of which are functional, and one of which has novel behaviors. As the number of human CYP11B genes was unknown and as the existence of novel P450c11 isozymes might have implications in the study of hypertension, we sought to determine if the human genome, like the rat genome, contained more than two CYP11B genes. Southern blotting of human genomic DNA digested with StuI suggested the existence of at least four human CYP11B genes. Similar analysis of cosmid clones suggested multiple CYP11B genes. However, cloning and sequencing of the multiple hybridizing fragments showed that there are only two CYP11B genes in the human genome, and that the "extra" bands seen were due to spurious hybridization. The absence of additional CYP11B genes in the human genome analogous to those in the rat narrows the search for genes that contribute to low renin hypertension.


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