护骨素基因T149C多态性对应用糖皮质激素患者骨量的影响

Effect of T149C polymorphism of osteoproteger in gene on bone mass in patients with glucocorticoid administration

目的探讨应用糖皮质激素患者护骨素(osteoprotegerin,OPG)基因启动子T149C单核苷酸多态性与骨密度和骨生化指标的相关性。方法应用聚合酶链反应限制性片断长度多态性(PCRRELP)方法测定126例正常健康人(Ⅰ组)和138例应用大量糖皮质激素的患者(Ⅱ组)护骨素基因启动子T149C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发现TT、TC、CC3种基因型,各基因型分布频率Ⅰ组为TT81.75%、TC16.67%、CC1.58%,Ⅱ组为TT82.61%、TC15.94%、CC1.45%,两组间无明显差异(P>0.05)。Ⅱ组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)gcm2,TC+CC(0.87±0.08)gcm2。经年龄、体重指数等因素校正后,差异仍有明显意义(P<0.05)。Ⅰ组的各项指标和Ⅱ组的其他指标在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基因型在两组间无明显差异,它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骨量的丢失有关。

Objective To investigate the effect of polymorphism（ T149C ）of promoter region of osteoprotegerin （OPG） gene on bone mineral density（BMD） and markers of bone turnover in patients using glucocorticoid. Methods The T149C genotypes of OPG promoter region were determined by PCR-RFLP in 126 healthy persons （group Ⅰ ） and 138 patients using a large dose of glucocorticolid （ group Ⅱ ）, and BMD at lumbar spine, femoral neck, trochanter and Ward＇s triangle etc, were measured by dual-energy X-ray absorptiometry（DEXA）. Markers of bone turnover were also detected. Results Hardy-Weinberg equilibrium was evident for OPG polymorphism. The frequency of the genotype was as following：TY 81.75% ,TC 16.67% and CC 1.58% in group Ⅰ ; IT 82.61%, TC 15.94 % and CC 1.45 % in group Ⅱ . No significant difference was found between the two groups（ P 〉 0.05）. In group Ⅱ ,the BMD at femoral neck area was （0.91 ± 0.06） g/cm^2, （0.87 ± 0.08）g/cm^2 of TT, TC ＋ CC genotypes respectively ,among which a significant difference was boserved （P 〈 0.05 by ANOVA）, and significant difference also presented after adjustment of age and BMI, but not in other markers. In group Ⅰ , no significant link was observed between OPG polymomphism and BMD with markers of bone turnover. Conclusions The genotype of OPG has no relationship with the onset of glomerulonephritis; while the polymorphism（T149C）in OPG gene may have effect on the BMD of femur neck in patients using hormone. Allele T may be the protection factor of bone mas which might be related to the loss of bone mass after medication of glucocortcoid.