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Genetic polymorphisms of CYP3A4 among Chinese patients with steroid-induced osteonecrosis of the femoral head.

ABSTRACT: Steroid therapy has been an important reason of nontraumatic osteonecrosis of the femoral head (ONFH). Steroids are metabolized by hepatic cytochrome P4503A, a low endogenous activity of this enzyme can contribute to the pathogenesis of ONFH. The aim of this study was to investigate the associations of polymorphisms of cytochrome P4503A4 (CYP3A4) gene with steroid-induced ONFH in Chinese patients.A total of 150 steroid-induced ONFH patients and 250 healthy controls were enrolled. We evaluated 5 single-nucleotide polymorphisms of the CYP3A4 gene in this case-control study.We identified rs2242480 in the CYP3A4 gene that was potentially associated with an increased risk of steroid-induced ONFH in the allele model (P?=?0.023; odds ratio [OR]: 1.47; 95% confidence intervals [CI]: 1.05-2.04) and in the additive model (P?=?0.028; OR: 1.44; 95% CI: 1.04-1.99) adjusted age?+?gender. Furthermore, we also observed a protective effect of haplotype "TG" (P?=?0.025; OR: 0.69; 95% CI: 0.49-0.96) and a risk effect of haplotype "CG" (P?=?0.006; OR: 1.81; 95% CI: 1.19-2.77) of the CYP3A4 gene adjusted age?+?gender.These findings suggested that polymorphisms of CYP3A4 gene may be associated with susceptibility to steroid-induced ONFH.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5591163 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Genetic polymorphisms of CYP3A4 among Chinese patients with steroid-induced osteonecrosis of the femoral head.

Wang Yuan Y Li Xiuling X Gao Yaoyu Y Li Zhi Z Yu Lidong L Meng Qingbo Q Sun Li L Wang Jianzhong J

Medicine 20161101 44

<h4>Background</h4>Steroid therapy has been an important reason of nontraumatic osteonecrosis of the femoral head (ONFH). Steroids are metabolized by hepatic cytochrome P4503A, a low endogenous activity of this enzyme can contribute to the pathogenesis of ONFH. The aim of this study was to investigate the associations of polymorphisms of cytochrome P4503A4 (CYP3A4) gene with steroid-induced ONFH in Chinese patients.<h4>Methods</h4>A total of 150 steroid-induced ONFH patients and 250 healthy cont ...[more]

PMID: 27858915

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Project description:Steroid-induced osteonecrosis of the femoral head (ONFH) is the most common clinical nontraumatic ONFH. Once ONFH occurs, it seriously reduces patients' quality of life. The matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) system was found to play a significant role in the development of ONFH. The aim of this study was to identify the associations between 7 genes selected from the MMP/TIMP system and steroid-induced ONFH.We genotyped 34 single-nucleotide polymorphisms (SNPs) of 7 genes selected from the MMP/TIMP system in a case-control study with 285 cases of steroid-induced ONFH and 308 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis.We found that the minor alleles of rs1940475 and rs11225395 in MMP8 were associated with a 1.32-fold increased risk of steroid-induced ONFH in the allelic model analysis (P?=?0.021 and 0.022, respectively). In the genetic model analysis, we found that rs3740938, rs2012390, rs1940475, and rs11225395 were associated with an increased risk of steroid-induced ONFH. In further stratification analysis, rs3740938 and rs2012390 displayed a significantly increased risk of steroid-induced ONFH in females under the dominant (rs3740938, OR?=?2.69, 95% CI: 1.50-4.83, P?=?0.001; rs2012390, OR?=?2.30, 95% CI: 1.31-4.03, P?=?0.012) and additive (rs3740938, OR?=?2.02, 95% CI: 1.24-3.29, P?=?0.010; rs2012390, OR?=?1.77, 95% CI: 1.12-2.80, P?=?0.047) models. In addition, haplotype "AGTCA" of MMP8 was found to be associated with a 1.40-fold increased risk of steroid-induced ONFH (95% CI: 1.04-1.88, P?=?0.025).Our results verify that genetic variants of MMP8 contribute to steroid-induced ONFH susceptibility in the population of northern China. In addition, we found that gender differences might interact with MMP8 polymorphisms to contribute to the overall susceptibility to steroid-induced ONFH.

Dataset Information

Genetic polymorphisms of CYP3A4 among Chinese patients with steroid-induced osteonecrosis of the femoral head.

Publications

Genetic polymorphisms of CYP3A4 among Chinese patients with steroid-induced osteonecrosis of the femoral head.

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