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Association of Single Nucleotide Polymorphisms in a Disintegrin and Metalloproteinase 12 Gene With Susceptibility to Knee Osteoarthritis: A Meta-Analysis.

ABSTRACT: Objectives This study aims to investigate the association between a disintegrin and metalloproteinase 12 polymorphisms and susceptibility to knee osteoarthritis (OA) through a meta-analysis involving only studies that present original data. Materials and methods A meta-analysis was performed on the association between a disintegrin and metalloproteinase 12 rs3740199, rs1871054, rs1278279 and rs1044122 polymorphisms and knee OA. An electronic search of all relevant studies published up to January 2017 was conducted using MEDLINE and EMBASE. The study included six case-control studies including 2,966 patients (850 males, 2,116 females) with knee OA and 4,901 controls (2,286 males, 2,615 females). Results No significant association was found between the rs3740199, rs1278279, and rs1044122 polymorphisms and knee OA when all studies were pooled into the meta-analysis. However, a significant association was found between the rs1871054 polymorphism and the knee OA risk (allele contrast: odds ratio (OR)=1.42, 95% confidence interval (CI)=1.02-1.98, p=0.04; dominant: OR=1.36, 95% CI=1.02-1.82, p=0.04; recessive: OR=1.83, 95% CI=1.14-2.94, p=0.01; and addictive model: OR=1.85, 95% CI=1.06-3.23, p=0.03). In the subgroup analysis, a significant association was found between the recessive (OR=0.44, 95% CI=0.21-0.93, p=0.03) and addictive model (OR=0.29, 95% CI=0.12–0.69, p<0.01) in the male group. Conclusion Our meta-analysis suggests that the rs1871054 polymorphism is associated with susceptibility to knee OA and that the GG genotype of rs3740199 was associated with knee OA in the male group. Additional well-designed studies are required to confirm these results.

SUBMITTER: JUNG J

PROVIDER: S-EPMC6542201 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Project description:Osteoarthritis (OA) is a complex disorder characterized by degenerative articular cartilage and is largely attributed to genetic risk factors. Single nucleotide polymorphisms (SNPs) are common DNA variants that have shown promising and efficiency, compared with positional cloning, to map candidate genes of complex diseases, including OA. In this study, we aim to provide an overview of multiple SNPs from a number of genes that have recently been linked to OA susceptibility. We also performed a comprehensive meta-analysis to evaluate the association of SNP rs7639618 of double von Willebrand factor A domains (DVWA) gene with OA susceptibility. A systematic search of studies on the association of SNPs with susceptibility to OA was conducted in PubMed and Google scholar. Studies subjected to meta-analysis include human and case-control studies that met the Hardy-Weinberg equilibrium model and provide sufficient data to calculate an odds ratio (OR). A total of 9500 OA cases and 9365 controls in 7 case-control studies relating to SNP rs7639618 were included in this study and the ORs with 95% confidence intervals (CIs) were calculated. Over 50 SNPs from different genes have been shown to be associated with either hip (23), or knee (20), or both (13) OA. The ORs of these SNPs for OA and the subtypes are not consistent. As to SNP rs7639618 of DVWA, increased knee OA risk was observed in all genetic models analyzed. Specifically, people from Asian with G-allele showed significantly increased risk of knee OA (A versus G: OR?=?1.28, 95% CI 1.13-1.46; AA versus GG: OR?=?1.60, 95% CI 1.25-2.05; GA versus GG: OR?=?1.31, 95% CI 1.18-1.44; AA versus GA+GG: OR?=?1.34, 95% CI 1.12-1.61; AA+GA versus GG: OR?=?1.40, 95% CI 1.19-1.64), but not in Caucasians or with hip OA. Our results suggest that multiple SNPs play different roles in the pathogenesis of OA and its subtypes; SNP rs7639618 of DVWA gene is associated with a significantly increased risk of knee OA in Asians. Given the limited sample size, further studies are needed to evaluate this observation.

Project description:INTRODUCTION:The role of genetic factors influencing osteoarthritis (OA) susceptibility is well documented and several candidate genes have been identified to be associated with it. Among these genes are Bone Morphogenetic Protein 5 (BMP5) and Smad family member 3 (SMAD3), all involved in Transforming Growth Factor (TGF) signaling pathway. The knee is the commonly affected joint, and knee OA has an especially high prevalence in Asian population. AIM:To investigate associations between Single Nucleotide Polymorphisms (SNPs) rs12901499 in SMAD3 and rs921126 in the BMP5 gene with knee OA susceptibility in and around Lucknow, Uttar Pradesh, India. MATERIALS AND METHODS:SNPs rs12901499 in SMAD3 and rs921126 in BMP5 were genotyped in patients with knee OA and age- sex matched OA-free controls from our population. A total of 450 patients with knee OA and 458 controls were enrolled in the study. Venous blood samples were obtained from all cases as well as controls for PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism). Data was collected and entered in excel sheets. Statistical analyses of the data were performed using statistical software package SPSS version 16.0. Chi-square, Student's t-test and logistic regression tests were used to analyse the data. RESULTS:GA and GG genotypes of both SNPs (rs12901499 and rs921126), and variant G, were associated with a significantly increased risk of knee OA. A significantly increased risk of knee OA was associated with the genotype GG and GA of rs12901499 (p < 0.03 and p <0.004 respectively) and rs921126 (p< 0.0001 and p<0.001 respectively) compared with the AA genotype. In addition, those bearing at least one G allele (GG + GA) had a significantly increased risk of knee OA compared with those without the G allele (AA) in rs921126 (p< 0.0001). However, in rs12901499, significant association with the risk of knee OA was not found (p<0.4). On age and gender based stratification, the association between the risk of OA and rs921126 GG mutant compared with AA homozygotes was strong in both gender (adjusted OR= 2.93 for male and 2.25 for female) and in those aged >55 years (adjusted OR= 3.4), similarly in rs12901499, GG mutant compared with AA homozygote was strong in female (adjusted OR= 1.5) and in those aged >55 years (adjusted OR= 1.5). CONCLUSION:The results showed that both in SMAD3 rs12901499 and BMP5 921126, G allele is significantly associated with knee OA. A to G change and variant G genotype may contribute to knee OA risk in our study population of Lucknow.

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Association of Single Nucleotide Polymorphisms in a Disintegrin and Metalloproteinase 12 Gene With Susceptibility to Knee Osteoarthritis: A Meta-Analysis.

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