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

Department of Internal Medicine, Room Ee585, Erasmus Medical Center, Dr. Molewaterplein 40, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 09/2005; 90(9):5313-6. DOI: 10.1210/jc.2005-0307
Source: PubMed


CYP3A7, expressed in the human fetal liver and normally silenced after birth, plays a major role in the 16alpha-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.
The objective of this study was to examine the effect of the CYP3A7*1C polymorphism on serum steroid hormone levels.
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.
Serum DHEA(S), androstenedione, estradiol, estrone, and testosterone levels were the main outcome measures.
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 micromol/liter (P = 0.02); study group 2, 2.09 +/- 0.08 vs. 1.08 +/- 0.12 micromol/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).
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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    • "The diminished effects in models 3 and 4 might be a consequence of the adjustment for precursor hormones with a circadian rhythm, as p-values remain similar in a model without the precursor hormone . As was previously put forward [33], a short half-life of DHEA and thus a high metabolic clearance rate [34] can explain the fact that no differences were found for mean DHEA levels among genotypes . Since there are strong correlations between DHEA, DHEAS and androstenedione [35] these might explain the significant difference observed for CYP3A7 genotypes. "
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