应用糖皮质激素患者护骨素基因T950C多态性与骨量的关系

Relationship between T950C polymorphism of osteoprotegerin gene and bone mass in patients undertaking glucocorticoid treatment

目的:分析应用糖皮质激素患者护骨素基因启动子T950C单核苷酸多态性与骨密度及骨生化指标的相关性。方法:选择2004-03/2005-06在哈尔滨医科大学附属第二医院肾内科就诊的应用糖皮质激素六七个月的慢性肾小球肾炎患者138例,另外选择126例门诊健康体检者作为正常对照组,调查和取样均征得两组受试者本人同意。应用聚合酶链反应-限制性片断长度多态性方法测定两组观察对象护骨素基因启动子T950C的基因型;应用双能X射线骨密度仪测定两组观察对象股骨、腰椎等部位的骨密度;同时检测骨代谢生化指标,测定血清骨钙素应用放射免疫法,测定甲状旁腺激素应用化学发光法。结果:进入结果分析应用激素组138例,正常对照组126例。①两组观察对象护骨素基因型的分布:启动子T950C发现TT、TC、CC3种基因型,各基因型分布频率正常对照组为TT26.98%,TC48.41%,CC24.61%,应用激素组为TT27.54%,TC48.55%,CC23.91%,两组间比较差异无显著性意义(P>0.05)。②T950C不同基因型观察对象骨密度、生化指标的比较:正常对照组3种基因型之间骨密度比较,差异无显著性意义(P>0.05);应用激素组各部位骨密度呈现CC>TC>TT的趋势,但差异无显著性意义(P>0.05)。两组各基因型之间骨代谢生化指标的差异均无显著性意义(P>0.05)。结论:应用糖皮质激素患者的护骨素基因T950C基因型与正常人群比较无明显差异,提示护骨素基因T950C基因型与肾小球肾炎的发病无关;护骨素基因T950C多态性与各部位骨密度无明显相关,推测可能与应用糖皮质激素后的骨量丢失无关。

AIM： To analyze the correlation of polymorphism （T950C） of promoter region of osteopmtegerin （OPG） gene with bone mineral density （BMD） and markers of bone biochemical index in patients using glucocorticoid. METHODS： Totally 138 patients with chronic glomerulonephritis, who used glucocorticoid for 6 or 7 months, were enrolled from Department of Nephrology, Second Affiliated Hospital, Harbin Medical University between March 2004 and June 2005. In addition, 126 people who made health examination at out-patient clinic were selected as normal control group. Testees of the two groups all agreed to joint the investigation and getting sampies. The T950C genotypes of OPG promoter region were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR- RFLP） in 126 healthy persons and 138 patients. BMD at femur and lumbar spine, etc. was detected with dual-energy X-ray absorptiometry （DEXA）. Meanwhile, biochemical index of bone metabolism was detected. Serum osteocalcin was tested with radio-immunity method. Parathyroid hormone was measured with chemiluminescence method. RESULTS： A total of 138 cases in the hormone group and 126 cases in the normal control group were involved in the result analysis. ①Distribution of genotypes of OPG of testees in the two groups： TT, TC and CC genotypes were found in promotor T950C, Frequencies of distribution of every genotype were TT26.98% ,TC48.41% and CC24.61%, respectively in the normal control group, and TT27.54% ,TC48.55% and CC23.91% in the hormone group, There was insignificant difference in the two groups （P 〉 0.05））. ②Comparison of BMD and biochemical index in different genotype of T950C. It had insignificant difference in the comparison of BMD in the three genotypes in the normal control group （P 〉 0.05）. Tendency of CC 〉 TC 〉 TT was showed in the BMD of every part in the hormone group, but had insignificant difference （P 〉 0.05）. Difference of biochemical index of bone metabolism in every genotype of the two groups was insignificant （P 〉 0.05）. CONCLUSION： The frequency of the genotype is insignificant difference between the T950C genotype of 0PG gene in glucocorticoid patients and normal people, which indicates that the T950C genotype of OPG gene has no relation with the episode of glomerulonephritis; Polymorphism of the T950C genotype of OPG gene has insignificant correlation with BMD at every part. It is suspected that maybe has no relationship with the loss of bone mass after applying glucocorticoid.