护骨素基因C1217T多态性与糖皮质激素性骨质疏松症的相关关系

OPG Gene C1217T Polymorphism and Glucocorticoid Induced Osteoporosis

目的探讨我国应用糖皮质激素患者护骨素(osteoprotegerin,OPG)基因内含子C1217T单核苷酸多态性与糖皮质激素性骨质疏松症(glucocorticoid-induced osteoporosis,GIO)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208例正常健康人(Ⅰ组)、168例非GIO患者(Ⅱ组)和104例GIO患者(Ⅲ组)护骨素基因内含子C1217T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。结果内含子C1217T发现CC、CT、TT3种基因型,GIO组基因型CC频率显著低于正常对照组,CT和TT基因型频率显著高于正常对照组;非GIO组、应用激素组(GIO组+非GIO组)与正常对照组比较各基因型频率均无统计学差异。正常对照组OPG基因C1217T的CC基因型组各部位的骨密度有高于CT和TT基因型组的趋势,但无统计学差异。非GIO组和GIO组OPG基因C1217T的CC基因型组腰椎的骨密度明显高于CT和TT基因型组(P<0.05),分别为非GIO组CC(1.01±0.17)g/cm2,CT+TT(0.99±0.07)g/cm2;GIO组CC(0.93±0.12)g/cm2,CT+TT(0.81±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)。结论OPG基因C1217T基因型在正常人和应用激素患者(Ⅱ、Ⅲ组)之间无明显差异,它可能与肾小球肾炎的发病无关;C1217T基因型在GIO组和正常对照组之间有明显差异,它可能与糖皮质激素性骨质疏松症的发病有关;OPG基因C1217T多态性与应用糖皮质激素患者(Ⅱ、Ⅲ组)腰椎的骨密度明显相关,等位基因C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. The aim of this study was to evaluate the association of C1217T polymorphism in osteoprotegerin （OPG） gene with Glucocorticoid- induced osteoporosis（GIO） in Chinese population. Methods：The C1217T genotypes of OPG were determined by PCR - RFLP in 208 healthy persons（group Ⅰ ）, 168 non - GIO patients （group Ⅱ ）and 104 patients with GIO（group ）. Bone mineral density（BMD） at lumbar spine, femoral neck, trochanter and Ward＇ s triangle were measured by dual - energy X -ray absorptiometry（DEXA）. Results： Hardy- Weinberg equilibrium was evident for OPG polymorphism. The frequency of OPG gene CC genotype was lower in group Ⅲ as compared with group Ⅰ , The frequency of CA2 and TT genotype was higher in group as compared with group Ⅰ . There were no significent difference of CC,CT and TT genotypes frequency in group Ⅱ and group Ⅱ ＋ （patients using a large dose of glucocorticoid） as compared with group I . The general BMD of the CA2 genotype of C1217T in group Iwas higher than that with CT and TT genotype but didn＇ t reach a significent level. BMD of lumbar spine of patients using a large dose of glucocorticoid was higher in genotype CC as compared with group CT ＋ TT（P 〈 0.05）. In group Ⅱ, the mean BMD at lumbar spine area was（1.01 ±0.17）g/cm^2,（0.99±0.07）g/cm^2 of the CC, CT ＋ TT genotypea respectively. In grouplⅡ ,the mean BMD at lumbar spine area was（ 0.93 ± 0.12）g/cm^2, （ 0.81 ± 0.08 ）g/cm^2 of the CC, CT ± TT genotypes respectively. The significant difference was also present after adjusted by age and BMI. Condusion： There is no significant difference of the C1217T genotype frequency between group Ⅰ and group Ⅱ ＋ Ⅲ, indicating that it might not be related with the onset of glomerulonephritis. The differenced the C1217T genotype frequency was significent between group I and group Ill, indicating that it might be related with the onset of glucocorticoid induced- osteoporosis. Pdymorphism of the OPG gene（C1217T） may have an effect on the BMD of ltanhar spine in the patients using glucocorticoid （ group Ⅱ ＋ Ⅲ ）, Allele C may be the protective factor of bene mass, and may have possible relationship with the loss of bene mass after using gluccoorticoid. KEY WORDS Glucocorticoid Bone mineral density Single nucleotide Polymorphism