Bácsi K, Kósa J P, Borgulya G, Balla B, Lazáry A, Nagy Z, Horváth C, Speer G, Lakatos P
1st Department of Medicine, Semmelweis University Budapest, 1083 Korányi S. u 2/a, Budapest, Hungary.
Calcif Tissue Int. 2007 Mar;80(3):154-9. doi: 10.1007/s00223-006-0227-8. Epub 2007 Mar 3.
The CYP3A7 enzyme metabolizes some steroid hormones, including dehydroepiandrosterone sulfate (DHEAS). The age-related decline of serum DHEAS levels is believed to contribute to osteoporosis. Previously, the CYP3A71C polymorphism has been shown to cause a persistent high CYP3A7 enzyme activity, resulting in lower levels of DHEAS in men. We hypothesized that the CYP3A71C polymorphism might contribute to bone loss through decreased levels of serum DHEAS in postmenopausal women. Postmenopausal women (n = 319) were divided into two subgroups: 217 with osteoporosis and 102 healthy controls. Genotyping, serum DHEAS measurement, and osteodensitometry of the lumbar spine and femoral neck were carried out in all subjects. Homozygous CYP3A71C carriers had significantly lower BMD at the lumbar spine compared to wild types (T score -3.27 +/- 1.02 in CYP3A71C homozygous mutants vs. -1.35 +/- 1.53 in wild types, P = 0.041). This association remained significant after adjustment for menopausal age, serum DHEAS level, alcohol consumption, steroid intake, smoking habits, and previous fractures. No association was found between genotypes and serum DHEAS levels in the total study population or in the subgroups. Serum DHEAS levels correlated positively with bone mineral density at the lumbar spine (r = 0.59, P = 0.042) after correction for age. Our data suggest that the CYP3A7 polymorphism might have an influence on bone mass at the lumbar spine independently of serum DHEAS concentrations.
细胞色素P450 3A7（CYP3A7）酶可代谢某些类固醇激素，包括硫酸脱氢表雄酮（DHEAS）。血清DHEAS水平随年龄下降被认为与骨质疏松症有关。此前研究表明，CYP3A71C基因多态性可导致CYP3A7酶活性持续升高，致使男性体内DHEAS水平降低。我们推测，CYP3A71C基因多态性可能通过降低绝经后女性血清DHEAS水平而导致骨质流失。将绝经后女性（n = 319）分为两个亚组：217例患有骨质疏松症，102例为健康对照。对所有受试者进行基因分型、血清DHEAS测量以及腰椎和股骨颈骨密度测定。与野生型相比，CYP3A71C纯合携带者的腰椎骨密度显著降低（CYP3A71C纯合突变体的T值为-3.27±1.02，野生型为-1.35±1.53，P = 0.041）。在对绝经年龄、血清DHEAS水平、饮酒量、类固醇摄入量、吸烟习惯和既往骨折情况进行校正后，这种关联仍然显著。在整个研究人群或亚组中，未发现基因型与血清DHEAS水平之间存在关联。校正年龄后，血清DHEAS水平与腰椎骨密度呈正相关（r = 0.59，P = 0.042）。我们的数据表明，CYP3A7基因多态性可能独立于血清DHEAS浓度而影响腰椎骨量。
