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Significant association between RETN genetic polymorphisms and alcohol-induced osteonecrosis of femoral head.

ABSTRACT: BACKGROUND:Alcohol-induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol-induced ONFH in Chinese Han population. METHODS:A case-control study including 201 patients and 201 controls was designed. Seven single nucleotide polymorphisms (SNPs) in RETN gene and four SNPs in LDLR gene were genotyped using Agena MassARRAY platform. In allele model and genetic model, chi-square test and logistic regression were used to study the associations between these SNPs and ONFH susceptibility. In addition, the relationships between these SNPs, clinical phenotypes, and blood lipid level with one-way analysis of variance were analyzed. RESULTS:In the allele model, rs7408174 and rs3745369 in RETN were associated with increased risk of alcohol-induced ONFH, whereas rs34861192 and rs3219175 in RETN showed reduced risk of alcohol-induced ONFH. In the genetic model, rs7408174 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. Rs3745369 showed an increased risk in codominant model, recessive model, and log-additive model. Rs34861192 showed a decreased risk in codominant model, dominant model, and log-additive model, and rs3219175 showed a decreased risk in dominant model and log-additive model. The rs3745368 in RETN was associated with the clinical stage of the disease. CONCLUSION:These results suggest that RETN genetic polymorphisms are associated with the susceptibility of alcohol-induced ONFH in Chinese Han population.

SUBMITTER: Liu C

PROVIDER: S-EPMC6687866 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Significant association between RETN genetic polymorphisms and alcohol-induced osteonecrosis of femoral head.

Liu Chang C An Feimeng F Cao Yuju Y Wang Jiaqi J Tian Ye Y Wu Huiqiang H Wang Jianzhong J

Molecular genetics & genomic medicine 20190617 8

<h4>Background</h4>Alcohol-induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol-induced ONFH in Chinese Han population.<h4>Methods</h4>A case-control study including 201 patients and 201 controls was designed. Seven single nucleotide polymorphisms (SNPs) in RE ...[more]

PMID: 31207150

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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

Significant association between RETN genetic polymorphisms and alcohol-induced osteonecrosis of femoral head.

Publications

Significant association between RETN genetic polymorphisms and alcohol-induced osteonecrosis of femoral head.

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