CYP19基因多态性与绝经后骨质疏松症的关联性  

Correlation of CYP19 gene polymorphisms with postmenopausal osteoporosis in Chongqing Chinese Han women

作　　者：耿力[1] 杨洪昌[2] 陈仲[2] 肖虹[1] 姚珍薇[3] 

机构地区：[1]昆明医学院第一附属医院妇产科,昆明650032 [2]云南省第二人民医院创伤外科,云南省创伤救治中心,昆明650021 [3]重庆医科大学附属第一医院妇产科,重庆400016

出　　处：《第三军医大学学报》2010年第14期1534-1538,共5页Journal of Third Military Medical University

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。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 （P0.05）. 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 （P0.05）. 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 （P0.05）. But the SS genotype and the S allele frequencies of PMO group were significantly higher than those of control group at the L2-4 （P0.05）. 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 （P0.05）. Th

关 键 词：骨质疏松症 绝经后 细胞色素P450 19基因 遗传多态性 骨密度 

分 类 号：R681.02[医药卫生—骨科学] R711.51[医药卫生—外科学]