论文部分内容阅读
峰值骨密度是由遗传和环境因素及其相互作用共同决定的复杂性状。维生素D受体基因、雌激素α受体基因、白介素6基因、副甲状腺素基因、Ⅰ型胶原α2基因、骨钙素基因、α2巯基糖蛋白基因是与骨代谢相关的7个重要的候选基因。本研究旨在检测这7个候选基因之间的相互作用对中国女性峰值骨密度的影响。样本为中国上海的361个无关、健康的绝经前女性,均为汉族人,年龄为20~44岁。采用HologicQDR2000+双能X射线扫描仪对腰椎与髋部的骨密度进行了检测。采用聚合酶链式反应-限制性片段长度多态分析方法对每个个体的以下8个多态性标记位点进行基因分型:维生素D受体基因的ApaⅠ位点,雌激素α受体基因的PvuⅡ和XbaⅠ位点,白介素6基因的BsrBⅠ位点,副甲状腺素基因的BstBⅠ位点,Ⅰ型胶原α2基因的MspⅠ位点,骨钙素基因的HindⅢ位点,α2巯基糖蛋白基因的SacⅠ位点。采用二元方差分析对基因相互作用与骨密度的关系进行研究。结果表明,白介素基因和雌激素α受体基因(PvuⅡ)的相互作用对髋部(P=0.019)、转子间区(P=0.016)和股骨颈(P=0.019)的骨密度有显著作用。在这3个部位,GGPp基因型携带者比GGpp基因型携带者的骨密度值分别高出18.0%、19.5%和14.8%。另外观察到α2巯基糖蛋白基因与白介素6基因的相互作用对股骨颈骨密度有显著影响(P=0.046)。GGSS基因型携带者的股骨颈骨密度值比GGSs基因型携带者高出18.8%。该项群体水平的统计分析表明:对于中国女性峰值骨密度的遗传决定,白介素基因和雌激素α受体基因、α2巯基糖蛋白基因的相互作用显著。
Peak bone mineral density is a complex trait determined by both genetic and environmental factors and their interactions. Vitamin D receptor gene, estrogen α receptor gene, interleukin 6 gene, parathyroid hormone gene, collagen type Ⅰ α2 gene, osteocalcin gene, α2 thiol glycoprotein gene and bone metabolism related to seven important candidate genes . The aim of this study was to examine the effect of the interaction of these seven candidate genes on peak BMD in Chinese women. The sample was 361 unrelated, healthy premenopausal women in Shanghai, China, all Han Chinese, aged 20-44. Bone mineral density was measured in the lumbar spine and hip using a HologicQDR2000 + dual-energy X-ray scanner. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype the following 8 polymorphic loci for each individual: the Apa I site of the vitamin D receptor gene, the estrogen receptor α gene BsrBⅠ locus of interleukin 6, BstBⅠ locus of parathyroid hormone, MspⅠ locus of α2 gene of collagen type Ⅰ, HindⅢ locus of osteocalcin and SacⅠ of α2-mercapto-glycoprotein Site. Bivariate analysis of variance was used to investigate the relationship between gene interaction and bone mineral density. The results showed that the interaction between interleukin and estrogen receptor gene (PvuII) had a significant effect on the BMD of hip (P = 0.019), interlobular area (P = 0.016) and femoral neck (P = 0.019) In these three sites, the GGPp genotypes were 18.0%, 19.5% and 14.8% higher than the GGpp genotype respectively. In addition, it was observed that the interaction of α2-mercapto-glycoprotein gene and interleukin-6 gene had a significant effect on femoral neck BMD (P = 0.046). The femur neck BMD values of GGSS genotype carriers were 18.8% higher than those of GGSs genotype carriers. Statistical analysis of the population level showed that the genetic determinants of peak BMD in Chinese women were significantly associated with the interaction of the interleukin gene with the estrogen receptor alpha gene and the alpha2-mercapto-glycoprotein gene.