护骨素基因A163G多态性对应用糖皮质激素患者骨量的影响

Effect of A163G polymorphism of osteoprotegerin gene on bone mass in patients using glucocorticoid

目的探讨应用糖皮质激素患者护骨素(osteoprotegerin,OPG)基因启动子A163G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(PCR-RELP)方法测定哈尔滨医科大学附属第一医院肾内科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A163G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A163G发现AA、AG、GG3种基因型,各基因型分布频率在两组间差异无显著性(P>0.05);将应用激素组患者分为骨质疏松组和低骨密度组,各基因型在两组间差异有显著性(P<0.05)。Ⅱ组各基因型之间腰椎、股骨颈的骨密度差异有显著意义(P<0.05),分别为:腰椎AA(1.04±0.12)g/cm2、AG(0.98±0.09)g/cm2、GG(0.83±0.08)g/cm2,股骨颈AA(0.84±0.09)g/cm2、AG(0.75±0.07)g/cm2、GG(0.69±0.09)g/cm2。经年龄、体重指数等因素校正后,差异仍有显著性(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性(P>0.05)。结论OPG基因A163G基因型在两组间差异无显著性,它与肾小球肾炎的发病无关;A163G基因型在骨质疏松组和低骨密度组之间有明显差异,它与糖皮质激素性骨质疏松症的发病有关;OPG基因A163G多态性与应用激素患者腰椎、股骨颈的骨密度明显相关,等位基因A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（A163G） of promoter region of osteoprotegerin（0PG） gene on bone mineral density（BMD） and markers of bone turnover in patients using glucocorticoid. Methods The A163G genotypes of OPG promoter region were determined by PCR-RFLP in 208 healthy persons and 272 patients using a large dose of glucocorticoid, and BMD at lumbar spine, femoral neck, trochanter and Ward＇ triangle etc, were measured by dualenergy X-ray absorptiometry（DEXA）. Some markers of bone turnover were also detected. Results Hardy-Weinberg equilibrium was evident for OPG polymorphism. The frequency of the genotype had no significant difference between the two groups. According to bone mineral density of lumbar spine, patients using glucocorticoid were divided into osteopenia group and osteoporosis group, The frequency of the genotype was significantly different between the two groups. In group Ⅱ, the BMD at lumbar spine area was （1.04 ＋ 0. 12） g/cm^2, （0. 98 ＋0. 09） g/cm^2, （0. 83 ＋ 0. 08） g/cm^2 of AA, AG, GG genotypes respectively, the BMD at femoral neck area was （0. 84＋ 0. 09） g/cm^2, （0. 75＋0. 07） g/cm^2, （0. 69 ＋ 0. 09）g/cm^2 of AA, AG, GG genotypes respectively, among which a significant difference was observed（P〈0. 05 by ANOVA）, and the significant difference also presented after adjusted by age and BMI, but not found the significant difference in other markers. In group Ⅰ, significant link was not observed between OPG polymorphism and BMD with markers of bone turnover. Conclusion The frequency of the genotype was no significant difference between the two groups, it has no relationship with onset of glomerulonephritis. The frequency of the genotype is significantly different between osteopenia group and osteoporosis group, it has relationship with onset of glucocorticoid induced-osteoporosis, polymorphism（A163G） of OPG gene may have an effect on the BMD of femoral neck and lumbar spine of the patients using hormone. Allele A may be the protection factor of bone mass, it has possible relationship with the loss of bone mass.