基因多态性与糖皮质激素诱导性股骨头坏死的相关性meta分析

Genetic Polymorphism for Steroid-induced Osteonecrosis of the Femoral Head: A Meta-analysis

关键词:  股骨头坏死  糖皮质激素  基因多态性  激素诱导性股骨头坏死  meta分析

Key words:  osteonecrosis of the femoral head  glucocorticoid  gene polymorphism  steroid-induced osteonecrosis of the femoral head(SONFH)  meta-analysis

摘要:

目的 应用meta分析证实靶基因的多态性是否与糖皮质激素诱导性股骨头坏死（steroid-induced osteonecrosis of the femoral head，SONFH）发生相关。方法 检索PubMed、Embase、The Cochrane Library、Clinical Trial、CBM、万方、维普和CNKI等数据库中已发表的文章以获得适宜的研究，并以固定或者随机效应模型计算最终的OR值和95%置信区间（95%CI）。结果 检索共发现有37项研究包含41个与SONFH发生风险相关的基因多态性位点。选择含有≥3个适宜研究的多态性位点进入meta分析，纳入的多态性位点主要集中在3个基因即PAI-1、MTHFR和ABCB1。携带有PAI-1突变基因5G的患者应用糖皮质激素后易发生SONFH，但差异不具有统计学意义[OR=0.95，95%CI（0.54，1.67），P=0.85]。SONFH发生率在MTHFR突变型和野生型之间差异存在统计学意义[OR=0.69，95%CI（0.50，0.95），P=0.02]，携带有MTHFR 677T的患者较易发生SONFH。携带ABCB1 3435C等位基因者发生SONFH的风险更高，具有显著的统计学差异[OR=1.40，95%CI（1.11，1.76），P=0.005]；而ABCB1 G2677T/A位点的基因多态性与SONFH发生之间无明显的统计学差异[OR=1.32，95%CI（0.76，2.28），P=0.32]。结论 MTHFR C677T和ABCB1 C3435T基因的多态性与股骨头坏死的发生风险显著相关。

Abstract:

OBJECTIVE To investigate whether polymorphisms in target genes were associated with the risk of steroid-induced osteonecrosis of the femoral head(SONFH) through a meta-analysis. METHODS Searched for eligible published literature from data base like PubMed, Embase, The Cochrane Library, Clinical Trial, CBM, Wanfang Data, Vip Data and CNKI and calculated pooled odds ratio(OR) and 95% confidence interval(CI) using a fixed- or random-effects model. RESULTS Thirty-seven articles with 41 genes described the relationship between polymorphisms and SONFH were found. Meta-analyses were carried out for those SNPs with three or more eligible studies, which included four SNPs located in three genes (PAI-1, MTHFR, ABCB1). The meta-analysis revealed that the risk of SONFH increased in PAI-1 5G allele carriers after using steroid but with no statistical difference[OR=0.95, 95%CI(0.54, 1.67), P=0.85]. Statistical difference[OR=0.69, 95%CI(0.50, 0.95), P=0.02] were observed between wild type and mutant type of MTHFR. The risk of SONFH in MTHFR 677T carriers is higher. The risk of SONFH also increased higher in ABCB1 3435C carriers with significant statistical difference[OR=1.40, 95%CI(1.11,1.76), P=0.005], while the polymorphisms of ABCB1 G2677T/A were not associated with the obvious risk of SONFH[OR=1.32, 95%CI(0.76, 2.28), P=0.32]. CONCLUSION The MTHFR C677T and ABCB1 C3435T polymorphisms may be significant risk factors for SONFH.