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This version published online on June 28, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0307
A more recent version of this article appeared on September 1, 2005
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Submitted on February 11, 2005
Accepted on June 21, 2005

A Common Polymorphism in the CYP3A7 Gene is Associated With a Nearly 50a% Reduction in Serum DHEAS levels

PAULINE SMIT, RON H.N. van SCHAIK, MARLOES van der WERF, ANNEWIEKE W. van den BELD, JAN W. KOPER*, JAN LINDEMANS, HUIBERT A.P. POLS, ALBERT O. BRINKMANN, FRANK H. de JONG, and STEVEN W.J. LAMBERTS

Departments of Internal Medicine (P.S., A.W.v.d.B, J.W.K., H.A.P.P, F.H.d.J., S.W.J.L.), Clinical Chemistry (R.H.N.v.S., M.v.d.W, J.L.), Reproduction & Development (A.O.B.) and Epidemiology & Biostatistics (H.A.P.P.), Erasmus MC, Rotterdam, the Netherlands

* To whom correspondence should be addressed. E-mail: f.koper{at}erasmusmc.nl.

Context: CYP3A7, expressed in the human fetal liver and normally silenced after birth, plays a major role in the 16{alpha}-hydroxylation of DHEA, DHEAS, and estrone. Due to a replacement of part of the CYP3A7 promoter with a sequence identical to the same region in the CYP3A4 promoter (referred to as CYP3A7*1C), some individuals still express a variant of the CYP3A7 gene later in life.

Objective: To study the effect of the CYP3A7*1C polymorphism on serum steroid hormone levels.

Design/Setting/Participants: Two population-based cohort studies: study group 1 consisting of 208 subjects randomly selected from the Rotterdam Study, and study group 2 consisting of 345 elderly independently living men.

Main Outcome Measures: Serum DHEA(S), androstenedione, estradiol, estrone, and testosterone levels.

Results: In study group 1 and 2, heterozygous CYP3A7*1C carriers had almost 50% lower DHEAS levels compared with homozygous carriers of the reference allele (study group 1: 1.74 ± 0.3 µmol/l vs. 3.33 ± 0.2 µmol/l, P = 0.02, study group 2: 2.09 ± 0.08 vs. 1.08 ± 0.12, P < 0.001). No differences in circulating DHEA, androstenedione, estradiol or testosterone levels were found. However, in study group 2, serum estrone levels were lower in heterozygous CYP3A7*1C carriers compared with homozygous carriers of the reference allele (0.11 ± 0.002 vs. 0.08 ± 0.006 nmol/l, P < 0.001).

Conclusion: The CYP3A7*1C polymorphism causes the persistence of the enzymatic activity of CYP3A7 during adult life, resulting in lower circulating DHEAS and E1 levels.
Key words: DHEAS • CYP3A7 • CYP3A7*1C




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