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The genetic association between PON1 polymorphisms and osteonecrosis of femoral head: A case-control study.

ABSTRACT: The purpose of this study was to investigate the relationship between Paraoxonase-1 (PON1) gene rs662, rs854555 polymorphisms and osteonecrosis of the femoral head (ONFH) in Han population, northern China.Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of PON1 polymorphisms in 84 patients with ONFH and 96 healthy persons. ? test was used to compare distribution differences of genotype, allele, and haplotype between the case and control groups. The odds ratio (OR) and 95% confidence interval (CI) were calculated to reveal the effects of PON1 polymorphisms on risk of ONFH, and the results were adjusted using logistic regression analysis. The linkage disequilibrium and haplotype analysis were performed with haploview software.That people carrying AA genotype of rs662 were easier to be attacked by ONFH than GG genotype carriers (OR?=?2.53, 95% CI?=?1.05-6.07, P?=?.038). Meanwhile, the frequency of A allele in the case group was significantly higher than the controls and it was a risk factor for ONFH (OR?=?1.56, 95% CI?=?1.03-2.38, P?=?.038). The A-A haplotype frequency of rs854555-rs662 in PON1 was significantly correlated to the increased susceptibility to ONFH (OR?=?2.74, 95% CI?=?1.28-5.84).The rs662 polymorphism in PON1 may be associated with ONFH susceptibility, but not rs854555 in Han population, northern China. Additionally, haplotype is also a nonignorable risk factor.

SUBMITTER: Li JM

PROVIDER: S-EPMC5662370 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The genetic association between PON1 polymorphisms and osteonecrosis of femoral head: A case-control study.

Li Jian-Mei JM Li Yi Y Wang Lu L

Medicine 20171001 42

The purpose of this study was to investigate the relationship between Paraoxonase-1 (PON1) gene rs662, rs854555 polymorphisms and osteonecrosis of the femoral head (ONFH) in Han population, northern China.Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of PON1 polymorphisms in 84 patients with ONFH and 96 healthy persons. χ test was used to compare distribution differences of genotype, allele, and haplotype between the case and control groups. T ...[more]

PMID: 29049204

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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

The genetic association between PON1 polymorphisms and osteonecrosis of femoral head: A case-control study.

Publications

The genetic association between PON1 polymorphisms and osteonecrosis of femoral head: A case-control study.

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