Smit Pauline, van Schaik Ron H N, van der Werf Marloes, van den Beld Annewieke W, Koper Jan W, Lindemans Jan, Pols Huibert A P, Brinkmann Albert O, de Jong Frank H, Lamberts Steven W J
Department of Internal Medicine, Room Ee585, Erasmus Medical Center, Dr. Molewaterplein 40, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2005 Sep;90(9):5313-6. doi: 10.1210/jc.2005-0307. Epub 2005 Jun 28.
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.
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.
Serum DHEA(S), androstenedione, estradiol, estrone, and testosterone levels were the main outcome measures.
In study groups 1 and 2, heterozygous CYP3A71C 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 CYP3A71C 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.
CYP3A7在人类胎儿肝脏中表达，出生后通常沉默，在脱氢表雄酮（DHEA）、硫酸脱氢表雄酮（DHEAS）和雌酮的16α-羟化过程中起主要作用。由于CYP3A7启动子的一部分被与CYP3A4启动子相同区域的相同序列所取代（称为CYP3A7*1C），一些个体在生命后期仍会表达CYP3A7基因的变体。
本研究的目的是检测CYP3A7*1C多态性对血清类固醇激素水平的影响。
设计、地点、参与者：进行了两项基于人群的队列研究。研究组1由从鹿特丹研究中随机选取的208名受试者组成，研究组2由345名独立生活的老年男性组成。
血清DHEA（S）、雄烯二酮、雌二醇、雌酮和睾酮水平是主要观察指标。
在研究组1和2中，CYP3A71C杂合子携带者的DHEAS水平比参考等位基因纯合子携带者低近50%[研究组1，1.74±0.25对3.33±0.15微摩尔/升（P = 0.02）；研究组2，2.09±0.08对1.08±0.12微摩尔/升（P < 0.001）]。循环中的DHEA、雄烯二酮、雌二醇或睾酮水平未发现差异。然而，在研究组2中，CYP3A71C杂合子携带者的血清雌酮水平比参考等位基因纯合子携带者低（0.11±0.002对0.08±0.006纳摩尔/升；P < 0.001）。
CYP3A7*1C多态性导致CYP3A7在成年期酶活性持续存在，导致循环中DHEAS和雌酮水平降低。
