Beijing Chao-Yang Hospital, Affiliate of Capital Medical University, Beijing 100020, China.
Steroids. 2013 Apr;78(4):401-8. doi: 10.1016/j.steroids.2013.01.004. Epub 2013 Jan 25.
Glucocorticoid-induced osteonecrosis is a common and severe adverse event. We conducted a meta-analysis to investigate whether polymorphisms in target genes were associated with the risk of corticosteroid-induced osteonecrosis. Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model. There were 23 articles with 35 genes described the relationship between polymorphisms and glucocorticoid-induced osteonecrosis. 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 PAI-1 4G allele was associated with an increased risk of osteonecrosis compared with the 5G allele (combined studies: OR=1.932, 95% CI=1.145-3.261). The OR for the 4G/4G vs. 5G/5G genotype of PAI-1 was 3.217 (95% CI 1.667-6.209 with combined studies), The relative risk of osteonecrosis was increased in the 4G allele vs. 5G/5G and 4G/4G genotype vs. 5G allele, with odds ratios of 2.304 (95% CI=1.235-4.299) and 2.307 (95% CI=1.527-3.485) in combined studies, respectively. The ABCB1 C3435T genotype distributions available confirmed that the C allele increased osteonecrosis risk compared with the T allele (OR 1.668, 95% CI=1.214-2.293) and TT genotype (OR 2.946, 95% CI=1.422-6.101). There was no evidence for significant association between MTHFR C677T and ABCB1 G2677T/A polymorphisms and risk of osteonecrosis. Results of this meta-analysis indicate that the PAI-1 4G/5G and ABCB1 C3435T polymorphisms may be risk factors for osteonecrosis.
糖皮质激素诱导性骨坏死是一种常见且严重的不良反应。我们进行了一项荟萃分析，旨在研究靶基因中的多态性是否与皮质类固醇诱导性骨坏死的风险相关。从 PubMed 和 EMBASE 中搜索了符合条件的文献。使用固定或随机效应模型计算合并的优势比（OR）和 95%置信区间（CI）。有 23 篇文章描述了 35 个基因中的多态性与糖皮质激素诱导性骨坏死之间的关系。对于具有三个或更多合格研究的那些 SNP 进行了荟萃分析，其中包括三个基因（PAI-1、MTHFR、ABCB1）中的四个 SNP。荟萃分析显示，与 5G 等位基因相比，PAI-1 4G 等位基因与骨坏死的风险增加相关（合并研究：OR=1.932，95%CI=1.145-3.261）。PAI-1 的 4G/4G 与 5G/5G 基因型的 OR 为 3.217（合并研究的 95%CI 为 1.667-6.209）。与 5G/5G 和 4G/4G 基因型相比，4G 等位基因的骨坏死相对风险增加，OR 值分别为 2.304（95%CI=1.235-4.299）和 2.307（95%CI=1.527-3.485）。合并研究中可用的 ABCB1 C3435T 基因型分布证实，与 T 等位基因相比，C 等位基因增加了骨坏死的风险（OR 1.668，95%CI=1.214-2.293）和 TT 基因型（OR 2.946，95%CI=1.422-6.101）。MTHFR C677T 和 ABCB1 G2677T/A 多态性与骨坏死风险之间没有明显的关联。这项荟萃分析的结果表明，PAI-1 4G/5G 和 ABCB1 C3435T 多态性可能是骨坏死的危险因素。
