绝经后女性CYP19基因Val80及OPG基因A163G多态性与骨密度的相关性研究

探讨细胞色素P450 19 (CYP19) 基因Val80多态性及护骨素(OPG) 基因A163G多态性与绝经后女性骨密度 (BMD) 的关系。随机选择居住在重庆的绝经后女性200例, 采用多聚酶链反应-限制性片段长度多态性法检测Val80及A163G多态性, 采用Norland公司XR-46系列双能X线骨密度仪测量股骨近端及腰椎BMD。 200名绝经后女性中Val80基因型GG、GA及AA的频率分别为19.5％、44.5％及36.0％; A163G基因型GG、GC 及CC的频率分别为: 13.0％, 42.0％及45.0％; 基因型频率分布均符合Hardy-Weinberg平衡 (P＞0.05)。协方差分析及多元逐步回归分析显示CYP19基因第3外显子Val80多态性与绝经后女性BMD无相关性 (P＞0.05)。除大转子外, A163G位点AG/GG/AG+GG基因型者股骨颈、Ward’s三角及腰椎BMD均较AA基因型者低, A163G基因型与股骨颈、Ward’s三角及腰椎BMD有相关性 (P＜0.05)。OPG基因启动子区A163G多态性分布存在明显的种族差异, 且与绝经后女性BMD有一定关联, AA型对BMD具有一定的保护作用, G等位基因是BMD降低的危险因素。

Association between Val80 polymorphism of the CYP19 gene, A163G polymorphism of the OPG gene and bone mineral density in post-menopausal Chinese women

We investigated the association of the G/A polymorphism at Val80 of the cytochrome P450 family 19 (CYP19) gene, the A163G polymorphism of the osteoprotegerin (OPG) gene with bone mineral density (BMD) in 200 randomly selected postmenopausal women in Chongqing. Single nucleotide polymorphisms were detected by polymerase chain reac-tion-restriction fragment length polymorphism (PCR-RFLP). BMD of the proximal femur and lumbar spine (L2-4) was measured by NORLAND XR-46 dual-energy X-ray absorptiometer (DEXA). The frequencies of genotypes in these women were as follows: GG (19.5), GA (44.5%), AA (36.0%) for the Val80 polymorphism in CYP19; and AA (13.0%), AG (42.0%), GG (45.0%) for the A163G polymorphism in OPG. The distribution of genotype frequency was in Hardy-Weinberg equilibrium (P0.05). ANCOVA and multiple stepwise regression analysis showed the Val80 polymor-phism in the third exon of the CYP19 gene was not associated with the BMD in postmenopausal women (P0.05). Except for the trochanter region, BMD at the femoral neck, Ward's triangle, and L2-4 was lower in subjects with AG/GG/AG+GG genotypes than those with the AA genotype for the A163G polymorphism and A163G genotypes were associated with BMD at these skeletal regions in postmenopausal women (P0.05). A163G polymorphism resides in the promoter region of the OPG gene and its genotype distribution is significantly different among different ethnic groups. Our results indicate that the AA genotype might have some beneficial effect on BMD and the variant G allele might reduce BMD in postmenopausal women.