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背景:原发性骨质疏松症是多基因遗传性疾病,但是调节骨量的基因需进一步研究。目的:探讨护骨素基因启动子区基因多态性与中国北京地区绝经前后妇女骨密度之间的关系。设计:前瞻性调查研究。单位:北京协和医院。对象:选择2002-07在北京协和医院健康体检的495名北京地区无亲缘关系的汉族妇女,其中绝经前妇女为306名,年龄20～39岁,绝经后妇女(指自然停经1年以上者)为189名,年龄50～84岁。所有受试对象均对检测项目知情同意。方法:①骨密度测量:应用双能X线骨密度测量方法,观察对象均采取仰卧位,采用骨密度仪测量其后前位第1～4腰椎及股骨近端,包括股骨颈、Ward’s三角和大转子部位的骨密度值。②基因分型:提取两组受试对象外周血DNA,初步确定护骨素基因分型。并取部分PCR产物送上海博亚有限公司测序,验证基因型,观察两组受试对象护骨素基因型的分布频率及其与骨密度的关系,并用Logistic回归作病因学进一步分析观察绝经后妇女护骨素基因多态性与骨质疏松的关系。主要观察指标:①两组受试对象护骨素基因型的分布频率,及其与骨密度的关系。②绝经后妇女护骨素基因多态性与骨质疏松的关系。结果:纳入受试对象495名,全部进入结果分析。①两组受试对象OPG基因型和等位基因分布频率无明显差异,两组总体基因型分布频率依次为163A→G位点,AA型为70.1%,AG型为26.9%,GG型为3.0%;245T→G位点TT型为71.3%,TG型为25.9%,GG型为2.8%。绝经前妇女在163A→G位点,AA组在L2-4、股骨颈、Ward’s三角和大转子的骨密度低于GG+AG组,在245T→G位点,TT组与GG+TG组相比各部位的骨密度也低,但均无统计学差异(P>0.05)。绝经后妇女163位点AG+GG组在L2-4、股骨颈、Ward’s三角和大转子的骨密度均显著低于AA组(P<0.05);245位点TG+GG组在股骨颈、Ward’s三角和大转子的骨密度显著低于TT组(P<0.05)。②绝经后妇女163位点AG+GG组在L2-4、Ward’s三角是骨质疏松的危险因素(OR=2.045,2.956,P<0.05,95%可信限1.05-6.7),245位点TG+GG组在L2-4、Ward’s三角、大转子是骨质疏松的危险因素(OR=2.059,2.859,2.123,P<0.05,95%可信限1.04-6.5)。结论:北京地区绝经后妇女护骨素基因启动子区的163和245位点为变异型G等位基因时,股骨颈、Ward’s三角和大转子的骨密度较低,变异型G等位基因与绝经后妇女骨密度降低相关。
BACKGROUND: Primary osteoporosis is a polygenic hereditary disease, but genes that regulate bone mass require further investigation. Objective: To investigate the relationship between the gene polymorphism of osteoprotegerin promoter and the bone mineral density in postmenopausal women in Beijing, China. Design: Prospective investigation. Unit: Beijing Union Medical College Hospital. PARTICIPANTS: A total of 495 unmarried Han Chinese women were selected to undergo a physical examination at Peking Union Medical College Hospital in Beijing in 2002-07, including 306 premenopausal women aged 20-39 years. Postmenopausal women (who were naturally with a menopause for more than one year) 189, aged 50 to 84 years old. All subjects were informed of the test items. Methods: ①Bone density measurement: The dual-energy X-ray absorptiometry method was used. All the subjects were in supine position. The first to fourth lumbar vertebrae and the proximal femur were measured by bone densitometer. They included femoral neck, Ward’s triangle and Bone density at the greater trochanter. ② Genotyping: Two groups of subjects were extracted from peripheral blood DNA, initially determine the osteoprotegerin genotyping. And take some PCR products sent to the Hai Boya Co., Ltd. sequenced and verified genotypes observed two groups of subjects the distribution of osteoprotegerin frequency and its relationship with bone mineral density, and further analysis of the use of Logistic regression etiology postmenopausal Relationship between osteoprotegerin gene polymorphism and osteoporosis in women. MAIN OUTCOME MEASURES: ① The distribution frequency of osteoprotegerin in two groups and its relationship with bone mineral density. ② postmenopausal women with osteoprotegerin gene polymorphism and osteoporosis. Results: A total of 495 subjects were enrolled in the study, all of which were included in the result analysis. ① There was no significant difference in genotype and allele frequencies of OPG between the two groups. The distribution frequency of genotypes in the two groups was 163A → G, followed by 70.1% for AA, 26.9% for AG and 3.0 for GG %; Type TTT at 245T → G was 71.3%, TG was 25.9%, and GG was 2.8%. In the premenopausal women at 163A → G, the BMD of L2-4, femoral neck, Ward’s triangle and the greater trochanter in AA group was lower than that of GG + AG group. In the 245T → G locus, the BMD of TT group and GG + TG group Bone mineral density than all parts is also low, but no statistical difference (P> 0.05). The bone mineral density of the 163-site AG + GG group at L2-4, the femoral neck, Ward’s trigone and the greater trochanter in postmenopausal women at 163 sites were significantly lower than those in the AA group (P <0.05) The BMD of the triangle and the greater trochanter were significantly lower than those of the TT group (P <0.05). (2) The risk of osteoporosis was significantly higher in the post-menopausal women with AG-GG at point 163 (OR = 2.045,2.956, P <0.05, 95% CI = 1.05-6.7) + GG group in L2-4, Ward’s triangle, the greater trochanter is a risk factor for osteoporosis (OR = 2.059,2.859,2.123, P <0.05, 95% confidence limit 1.04-6.5). CONCLUSIONS: The BMDs of the femoral neck, Ward’s trigone and the greater trochanter are lower at sites 163 and 245 of the pro-Osteopontin promoter in postmenopausal women in Beijing, with variant G alleles and Postmenopausal women are associated with reduced bone mineral density.