降钙素受体基因多态性与原发性骨质疏松的相关性

Association between calcitonin receptor gene polymorphism and primary osteoporosis

目的:骨质疏松是多基因调控疾病,峰值骨量达到和骨量丢失均受遗传因素影响。观察山东半岛地区汉族人群降钙素受体Alu-Ⅰ基因多态性各基因型频率及其与骨质疏松的关系,探讨原发性骨质疏松症的遗传易感因素。方法:试验于2005-06/2007-06在青岛大学医学院附属医院中心实验室完成。①试验对象:选取332名长期居住在山东半岛地区无亲缘关系的汉族人群,纳入标准:健康门诊查体人员、原发性骨质疏松症及原发性骨质疏松症所致骨折患者;患者对试验知情同意。排除标准:各种继发性骨质疏松症;影响骨代谢相关疾病史;服用影响骨代谢药物等。其中骨质疏松合并骨折75例作为骨质疏松性骨折组,余257例经过骨密度测定确定骨量,按骨质疏松诊断标准(骨密度测定值比同性别峰值骨密度均值降低2.5个标准差)分为骨量正常组(n=201)及骨质疏松组(n=56)。②试验方法:应用聚合酶链反应限制性片段长度多态性分析技术测定257名山东半岛汉族成年人和75名骨质疏松性骨折患者降钙素受体基因型,用双能X射线吸收法测定腰椎、股骨颈、粗隆间、Ward’s三角和大转子区等部位的骨密度值。结果:纳入受试者332人,均进入结果分析。①本试验人群降钙素受体基因型频率分布均符合Hardy-Weinberg定律(χ2=0.47,P=0.493)。基因型频率分布依次为CC型占89.5%,CT型占10.5%,TT型占0%。②年龄与不同部位骨密度值之间呈负相关(P<0.01),体质量指数与骨密度值之间呈正相关(P<0.01),在将年龄和体质量指数进行校正后发现女性CC基因型较CT基因型在ward’s三角区有较高的骨密度(P<0.05),骨量正常组各基因型与骨质疏松性骨折组之间差异无显著性意义(P>0.05)。结论:山东半岛汉族女性降钙素受体基因型与骨密度之间存在一定关联,降钙素受体C1377T基因多态性可能成为胶东半岛汉族女性发生骨质疏松危险性的遗传标志。

AIM： Osteoporosis is a polygenic disease, and the peak bone mass and bone mass loss are significantly determined by genetic factors. The study determined the genotype frequencies of calcitonin receptor Alu Ⅰ gene polymorphism and its association with osteoporosis in Shandong peninsula Han populations, so as to explore the predisposing factor for osteoporosis in heredity. METHODS： The experiment was conducted in the central laboratory of Affiliated Hospital of Qingdao Medical College from June 2005 to June 2007. ①332 Han people from unrelated families who lived in Shandong peninsula for many years were selected. Those with healthy physical examination personnel from health clinic, primary osteoporosis and primary osteoporotic fracture were enrolled, and the informed consents were obtained from all the participants. All people with various secondary osteoporosis, bone metabolism disease, and drugs that had influence on bone metabolism were excluded. People with osteoporosis complicated by fracture served as osteoporotic fracture group （n =75）, and the rest were divided into normal bone mass group （n =201） and osteoporosis group （n =56） according to the body mass （bone densitometry was 2.5 standard deviation lower than peak bone density of the same sex）. ②Alu Ⅰ polymorphism of calcitonin receptor gene was tested by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） in 257 adults and 75 patients with osteoporotic fracture. The bone mineral density of lumbar spine （L2-4）, intertroch, femoral neck, Ward＇s triangle area and greater trochanter were measured by dual-energy X-ray absorptiometry （DEXA）. RESULTS： 332 subjects were all involved in the result analysis. ①The frequencies distribution of Alu Ⅰ alleles and genotypes in this cohort were accorded with Hardy-Weinberg equilibrium （ x^2 =0.47, P =0.493）. The frequency distribution of genotypes CC, CT and TT were 89.5%, 10.5% and 0%. ②Age showed significant negative correlation with bone mineral density （P 〈 0.01）, and body mass index had significant positive correlation with bone mineral density （P 〈 0.01）. The bone mineral density in Ward＇s triangle of women with CC genotype was significant higher compared with CT genotype （P 〈 0.05） after the body mass index and age were corrected. There was no significant difference between osteoporotic fracture group and normal control group （P 〉 0.05）. CONCLUSION： There is a possible correlation between calcitonin receptor gene polymorphisms and bone mineral density in Han female of Shandong peninsula. C1377T gene polymorphism may act as the genetic marker in predicting the risk factor for osteoporosis.