Zhang Yanqiong, Kong Xiangying, Wang Rongtian, Li Shangzhu, Niu Yanfang, Zhu Liuluan, Chen Weiheng, Lin Na
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing, 100700, China.
Mol Biol Rep. 2014 May;41(5):3135-46. doi: 10.1007/s11033-014-3173-y. Epub 2014 Jan 28.
Steroid administration, which is commonly performed for the treatment of autoimmune inflammatory diseases, cancers or organ transplantation, has been a leading cause of nontraumatic osteonecrosis of the femoral head (ONFH). Single nucleotide polymorphisms (SNPs) of the adenosine triphosphate-binding cassette B1 (ABCB1) gene have been demonstrated to be related to steroid-induced ONFH in small sample sizes of Japanese kidney failure and Chinese systemic lupus erythematosus patients. However, there are obvious controversial results in the relationship of ABCB1 gene polymorphisms with steroid-induced ONFH. The aim of this study was to validate the genetic association of ABCB1 polymorphisms with the risk for steroid-induced ONFH in a large cohort of Chinese population. A case-control study was conducted, which included 94 and 106 unrelated patients after steroid administration recruited from 14 provinces in China, respectively. Two SNPs (rs1045642 and rs2032582) within ABCB1 were genotyped using Sequenom MassARRAY system. Multivariate analyses based on clinical information were performed to determine the associations between the SNPs and risk of steroid-induced ONFH. rs1045642 SNP was significantly associated with steroid-induced ONFH group in codominant (P=0.02), recessive (P=0.006) and overdominant (P=0.03) models. However, there were no differences found in genotype frequencies of rs2032582 SNP between controls and patients with steroid-induced ONFH (all P>0.05). These findings suggested that rs1045642 SNP of ABCB1 may be associated with the risk of steroid-induced ONFH. Thus, it is useful to analyze this polymorphism for identifying high-risk individuals before the administration of steroids.
类固醇给药常用于治疗自身免疫性炎症疾病、癌症或器官移植，一直是股骨头非创伤性骨坏死（ONFH）的主要原因。在日本肾衰竭患者和中国系统性红斑狼疮患者的小样本研究中，已证明三磷酸腺苷结合盒B1（ABCB1）基因的单核苷酸多态性（SNP）与类固醇诱导的ONFH有关。然而，ABCB1基因多态性与类固醇诱导的ONFH之间的关系存在明显争议。本研究的目的是在一大群中国人群中验证ABCB1多态性与类固醇诱导的ONFH风险的遗传关联。进行了一项病例对照研究，分别纳入了从中国14个省份招募的94例和106例类固醇给药后的无亲缘关系患者。使用Sequenom MassARRAY系统对ABCB1内的两个SNP（rs1045642和rs2032582）进行基因分型。基于临床信息进行多变量分析，以确定SNP与类固醇诱导的ONFH风险之间的关联。rs1045642 SNP在共显性（P = 0.02）、隐性（P = 0.006）和超显性（P = 0.03）模型中与类固醇诱导的ONFH组显著相关。然而，在对照组和类固醇诱导的ONFH患者中，rs2032582 SNP的基因型频率没有差异（所有P>0.05）。这些发现表明，ABCB1的rs1045642 SNP可能与类固醇诱导的ONFH风险有关。因此，在给予类固醇之前分析这种多态性有助于识别高危个体。
