护骨素基因T149C、T950C多态性与糖皮质激素性骨质疏松症的关系

Relationship between the polymorphisms of T149C and T950C in osteoprotegerin gene and the glucocorticoid-induced osteoporosis

目的探讨应用糖皮质激素患者护骨素(osteoprotegerin,OPG)基因启动子T149C、T950C单核苷酸多态性与骨密度的相关性。方法应用聚合酶链反应-限制性片断长度多态性(PCR-RELP)方法测定哈尔滨医科大学附属第一医院208例正常健康人(Ⅰ组)和272例应用大量糖皮质激素的患者(Ⅱ组)护骨素基因启动子T149C、T950C的基因型;应用双能X线骨密度仪(DEXA)测定股骨、腰椎等部位的骨密度,同时检测骨代谢生化指标。结果启动子T149C、T950C均发现TT、TC、CC三种基因型,各基因型分布频率在两组间无明显差异(P>0.05)。Ⅱ组T149C各基因型之间股骨颈的骨密度差异有显著意义(P<0.05),分别为:TT(0.91±0.06)g/cm2,TC+CC(0.87±0.08)g/cm2。经年龄、体重指数等因素校正后,差异仍有明显意义(P<0.05)。Ⅱ组T950C各部位骨密度呈现CC>TC>TT的趋势,但差异无显著意义(P>0.05)。Ⅰ组的各部位骨密度和Ⅱ组的其他部委骨密度在T149C、T950C不同基因型间的差异均无显著意义(均P>0.05)。结论OPG基因T149C、T950C基因型在两组间无明显差异,它们可能与肾小球肾炎的发病无关;OPG基因T149C多态性与应用激素患者股骨颈的骨密度明显相关,等位基因T可能是骨量的保护因子,它可能与应用糖皮质激素后的骨量丢失有关;OPG基因T950C多态性与各部位骨密度无明显相关,它可能与应用糖皮质激素后的骨量丢失无关。

Objective To investigate the effect of polymorphisms of T149C and T950C in the promoter region of osteoprotegerin （OPG） gene on bone mineral density （BMD） in patients treated with glucocorticoids. Methods We determined T149C and T950C polymorphisms in the promoter region of OPG gene by PCR-RFLP in 208 healthy individuals （group 1） and 272 patients treated with large doses of glucocorticoids （group 2）. BMD at lumbar spine, femoral neck, trochanter and Ward＇s triangle were measured by dual-energy X-ray absorptiometry （DEXA）. Several markers relating to bone turnover were also assayed. Results Hardy-Weinberg equilibrium was evident to the two polymorphisms. T149C genotypes in group 1 were TT （81.75%）, TC （16.67%） and CC （1.58%）, and those in group 2 were TT （82.61%）, TC （15.94%） and CC （1.45%）. There is no significant difference in the distribution of T149C genotypes between the two groups （P〉0.05）. T950C genotypes in group 1 were TT （26.98%）, TC （48.41%） and CC （24.61%）, those in group 2 were TT （27.54%）, TC （48.55%） and CC （23.91%）. There is also no significant difference in the distribution of T950C genotypes between the two groups （p〉0.05）. In group 2, however, BMD at femoral neck area was （0.91 ± 0.06） g/cm^2 and （0.87 ± 0.08） g/cm^2 in patients carrying TT and TC＋CC of the T149C genotype, respectively （P〈0.05 by ANOVA）. This difference is still significant after adjustment by age and body weight index. In group 2, the correlation of T950C genotypes to the magnitude of BMD at all areas was CC 〉 TC 〉 TT, but this correlation is statistically insignificant （P〉0.05）. In group I, no correlation of the genotypes T149C and T950C to the magnitude of BMD was observed. Conclusions There are no differences in the distribution of T149C and T950C genotypes in OPG gene between the two groups. Therefore, these two polymorphisms may not be related to the pathogenesis of glomerulonephritis. The polymorphism T149C may relate to the BMD at femoral neck in patients treated with glucocorticoids, in which allele T may be the protection factor of bone mass and may involve in the loss of bone mass by glucocorticoids. The polymorphism T950C may have no effects on BMD at all areas, and may not involve in the loss of bone mass by glucocorticoids.