【摘要】 目的探讨细胞色素P450 19(CYP19)基因第3外显子缬氨酸(Val)80单核苷酸多态性及第4内含子(TTTA)n短串联重复序列多态性与绝经后骨质疏松症(postmenopausal osteoporosis,PMO)的关系。方法选取78例股骨颈PMO患者和122例对照以及108例腰椎(L2-4)PMO患者和92例对照分别进行病例对照研究,采用聚合酶链反应-限制性片段长度多态法检测Val80多态性,采用基因扫描及DNA测序技术检测(TTTA)n多态性,以TTTA重复序列中位数10次为界将重复序列基因分为短基因(<10)和长基因(≥10),分别以S和L表示,采用NORLAND公司XR-46系列双能X线骨密度仪测量股骨颈及L2-4骨密度。结果股骨颈及L2-4部位的各组基因型分布符合Hardy-Weinberg平衡(P>0.05)。Val80多态性:股骨颈及L2-4部位病例组和对照组基因型和等位基因频率分布无显著性差异(P>0.05);(TTTA)n多态性:在股骨颈部位,病例组和对照组基因型和等位基因频率分布无显著性差异(P>0.05),而L2-4部位,病例组SS基因型和S等位基因频率较对照组显著性升高(P<0.05)。调整年龄、绝经时间、绝经年龄及体质指数后,以这2个多态性位点作为自变量的多元Logistic回归显示仅(TTTA)n多态性与L2-4PMO显著相关,并独立于PMO传统危险因素,SS+SL基因型者患病风险较LL型者增高(adjustedOR2.246,95%CI1.070～4.715,P=0.032)。结论 CYP19基因(TTTA)n多态性与L2-4部位PMO独立关联,S等位基因显性影响PMO的发病风险,而CYP19基因Val80多态性与股骨颈及L2-4部位PMO的发生无显著相关。更多还原

【Abstract】 Objective To investigate the correlation of a G/A at Val80 in the third exon and a TTTA repeat polymorphism in the forth intron of cytochrome P450 family 19 (CYP19) gene with postmenopausal osteoporosis (PMO) in Chinese Han population. Methods A case-control study was carried out on 78 femoral neck PMO patients and 122 matched controls,and 108 lumbar spine (L2-4) PMO patients and 92 controls. Inclusion criteria,at the age of 41 to 65,Han nationality,living in Chongqing more than 10 years,with natural menopause over 1 year,no history of taking drugs affecting bone metabolism. Exclusion criteria: menopause too early (younger than 40 years old),secondary osteoporosis or disease affecting bone mineral density,or consanguinity. Genotypes for the Val80 polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes for the (TTTA)n polymorphism were determined by gene scan and DNA sequencing. The (TTTA)n <10 and (TTTA)n ≥10 alleles were designated S and L,respectively. Bone mineral density for the proximal femur and L2-4 was measured by NORLAND XR-46 dual-energy X-ray absorptiometry (DEXA). Results The genotype distribution in each group was met with Hardy-Weinberg equilibrium at each skeletal site (P>0.05). There was no significant difference in the genotype and allele distributions of Val80 polymorphism between PMO group and control group at the femoral neck and L2-4 sites (P>0.05). At the femoral neck site,there was no significant difference in the genotype and allele distributions of (TTTA)n polymorphism between PMO group and control group (P>0.05). But the SS genotype and the S allele frequencies of PMO group were significantly higher than those of control group at the L2-4 (P<0.05). After adjustments for age,years after menopause,menopausal age,and body mass index,Logistic regression analyses revealed only the (TTTA)n polymorphism remained significantly associated with PMO at the L2-4 (P<0.05). The subjects with the combined SS and SL genotype had higher risk of PMO compared with those with the LL genotype (adjusted OR=2.246,95% CI 1.070 to 4.715,P=0.032). Conclusion CYP19 (TTTA)n polymorphism is independently correlated with PMO at the L2-4 in Chongqing Chinese Han population. The presence of the S allele T may dominantly increase the risk of PMO at the L2-4. The data also suggest that the CYP19 Val80 polymorphism might not be associated with PMO.更多还原