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A Common Polymorphism in the CYP3A7 Gene Is Associated with a Nearly 50% Reduction in Serum Dehydroepiandrosterone Sulfate Levels

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 and Development (A.O.B.), and Epidemiology and Biostatistics (H.A.P.P.), Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. Jan W. Koper, Department of Internal Medicine, Room Ee585, Erasmus Medical Center, Dr. Molewaterplein 40, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. 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-hydroxylation of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and estrone. Due to a replacement of part of the CYP3A7 promoter with a sequence identical with 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: The objective of this study was to examine the effect of the CYP3A7*1C polymorphism on serum steroid hormone levels.

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

Main Outcome Measures: Serum DHEA(S), androstenedione, estradiol, estrone, and testosterone levels were the main outcome measures.

Results: In study groups 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 ± 0.25 vs. 3.33 ± 0.15 µmol/liter (P = 0.02); study group 2, 2.09 ± 0.08 vs. 1.08 ± 0.12 µmol/liter (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/liter; P < 0.001).

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

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