Dataset Information

Association between ADAM12 Single-Nucleotide Polymorphisms and Knee Osteoarthritis: A Meta-Analysis.

ABSTRACT: ADAM12 polymorphisms may be associated with the risk of knee osteoarthritis (KOA), but currently available evidence remains controversial. We performed this meta-analysis to confirm whether ADAM12 polymorphisms were associated with susceptibility of KOA.A comprehensive literature search in PubMed, EMBASE, and ISI Web of Science was conducted to identify observational studies assessing the association between ADAM12 polymorphisms and susceptibility of KOA. The strength of association was indicated as odds ratio (OR) and the corresponding 95% confidence interval (95%CI). Four types of genetic model (additive model, dominant model, recessive model, and allele model) were evaluated for each included study. Subgroup analysis by ethnicity was performed.Seven case-control studies comprising a total of 3512 KOA patients and 5405 healthy controls were included in the meta-analysis. A significant association between rs1871054 and increased KOA risk was found in each genetic model. No significant association was found between KOA and rs3740199, rs1044122, or rs1278279 in any genetic model.Based on the findings of our study, there was a modest but statistically significant association between rs1871054 and risk of KOA in Asian population, while other polymorphisms (rs3740199, rs1044122, or rs1278279) in ADAM12 were not associated with KOA in any population.

SUBMITTER: Lv ZT

PROVIDER: S-EPMC5591934 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Association between ADAM12 Single-Nucleotide Polymorphisms and Knee Osteoarthritis: A Meta-Analysis.

Lv Zheng-Tao ZT Liang Shuang S Huang Xiao-Jian XJ Cheng Peng P Zhu Wen-Tao WT Chen An-Min AM

BioMed research international 20170808

<h4>Objective</h4>ADAM12 polymorphisms may be associated with the risk of knee osteoarthritis (KOA), but currently available evidence remains controversial. We performed this meta-analysis to confirm whether ADAM12 polymorphisms were associated with susceptibility of KOA.<h4>Methods</h4>A comprehensive literature search in PubMed, EMBASE, and ISI Web of Science was conducted to identify observational studies assessing the association between ADAM12 polymorphisms and susceptibility of KOA. The st ...[more]

PMID: 28929114

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Project description:BackgroundOsteoarthritis of the knee is an irreversible disease that causes great pain, and genetic factors play an important role in its occurrence and development. There have been many studies on the correlation between ADAM12 polymorphisms and genetic susceptibility to osteoarthritis, but the results remain inconclusive.MethodsPapers from PubMed, Web of Science, EMbase, Springer, SCOPUS, Google Scholar and other databases were systematically retrieved with a cut-off of January 2022. All case-control studies on ADAM12 rs3740199, rs1871054, rs1044122, and rs1278279 polymorphisms and osteoarthritis were searched. Fixed or random effects models were used for pooled analysis with OR values and 95% confidence intervals (CI), and publication bias was assessed. In addition, the false-positive reporting probability test was used to assess the confidence of a statistically significant association.ResultsEleven articles were included, which included 3332 patients with osteoarthritis and 5108 healthy controls. Meta-analysis showed that the rs1871054 polymorphism of ADAM12 was associated with osteoarthritis in dominant, recessive, allelic, and homozygote genetic models [C vs. T: OR = 1.34 95% CI (1.05, 1.71), P < 0.001]. Our subgroup analysis revealed an association between the ADAM12 polymorphism rs1871054 in Asians and osteoarthritis [C vs. T: OR = 1.61, 95% CI (1.25, 2.08), P < 0.001], albeit this was only for three studies. In addition, the ADAM12 polymorphism rs1871054 is associated with osteoarthritis in patients younger than 60 years of age [C vs. T: OR = 1.39, 95% CI (1.01, 1.92), P = 0.289]; however, the ADAM12 gene rs3740199, rs1044122, and rs1278279 site polymorphisms were not significantly. Furthermore, when assessing the confidence of the positive results, the positive results were found to be credible (except for Age < 60).ConclusionPolymorphism at the rs1871054 site of ADAM12 is associated with genetic susceptibility to osteoarthritis, but rs3740199, rs1044122, and rs1278279 site polymorphisms are not.

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.

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.

Dataset Information

Association between ADAM12 Single-Nucleotide Polymorphisms and Knee Osteoarthritis: A Meta-Analysis.

Publications

Association between ADAM12 Single-Nucleotide Polymorphisms and Knee Osteoarthritis: A Meta-Analysis.

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