低体重与护骨素基因启动子T149-C和A163-G多态性与骨质疏松的关系

目的 探讨护骨素(OPG)基因启动子区T149-C和A163-G多态性及低体重联合作用对绝经后健康女性和绝经后骨质疏患者骨密度(BMD)的影响.方法 以134例广州地区居住10年以上无亲缘关系的绝经汉族女性为研究对象.骨质疏松症73例,绝经后健康女性61例作对照组.随机抽取25个样本经SSCP-PCR法寻找异常迁移条带,再采用测序方法确定扩增区域中的单核苷酸突变位点,最后采用PCR限制性片段长度法(RFLP)对所有样本进行分析;双能X线吸收法测定BMD.结果 在73例绝经后骨质疏松症女性和61例绝经后健康女性OPG启动子扩增区中,找到两个单核苷酸点突变多态性位点,T149-C和A163-G.分析显示这两个多态性位点基因型频率在两组中的分布均符合Hardy-Weinberg定律.T149-C和A163-G多态性单一基因型和复合基因型的频率分布在两组实验对象间差异无统计学意义(P＞0.05).对单一基因型及其复合基因型的BMD分析显示绝经后骨质疏松症女性的腰椎和髋部BMD明显低于绝经后健康女性.绝经后骨质疏松症患者的体质指数(BMI)也明显低于绝经后健康女性[分别为(22.5±3.0)kg/m2和(24.4±3.6)kg/m2,P＜0.01].结论 T149-C和A163-G多态性对绝经后骨质疏松患者和绝经后健康女性的骨量影响没有协同作用;单一的和复合的T149-C和A163-G多态性各基因型不能作为预测中国汉族女性发生骨质疏松的遗传标志,但可能是骨质疏松发生的易感基因.

The effect of low-body weight combined with T149-C and A163-G polymorphism of osteoprotegerin promoter region on osteoporosis

Objective To investigate the effect of T149-C and A163-G polymorphism of osteoprotegerin promoter region combined with low-body weight on bone mineral density (BMD) of postmenopausal osteoporosis women and postmenopausal healthy women. Methods Seventy-three postmenopausal osteoporosis women and 61 postmenopausal healthy women were enrolled. The shifted patterns were searched from randomly selected 25 samples by SSCP-PCR and their sequences were determined by cycle sequencing. The T149-C and A163-G polymorphisms were determined by PCR-RFLP. BMD of lumbar spines and femoral neck, Ward and trochanteric areas were measured by dual energy X-ray absorptiometry. Results T149-C and A163-G polymorphisms in the postmenopausal osteoporosis women and the postmenopausal healthy women were through Hardy Weinberg equilibrium. Both single and combined genotype frequencies of the T149-C and A163-G polymorphism did not show any difference between postmenopausal osteoporosis women and postmenopausal healthy women. The BMD levels of the postmenopausal osteoporosis women were significantly lower than those of the postmenopausal healthy women in lumbar spines and femoral neck, and BMI levels of the postmenopausal osteoporosis women was significantly lower than those of the postmenopausal healthy women. Conclusions The T149-C and A163-G polymorphism has no synergistic effect on bone mass in both the postmenopausal osteoporosis women and the postmenopausal healthy women. The single and combined genotypes of the T149-C and A163-G polymorphism may not be used as genetic markers in predicting their risk of developing osteoporosis in Chinese women of the Han nationality, but may be susceptible gene of osteoporosis.