title: Single Nucleotide Polymorphisms and Osteoarthritis: An Overview and a Meta-Analysis.
abstract: 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.
authors.affiliation: From the Center for Reproduction and Genetics (TW, HL, HL, QH, YX, CS, CZ, JX, JD, LQ), Suzhou Hospital affiliated to Nanjing Medical University, Suzhou, Jiangsu; Department of Laboratory Medicine (YL), Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai; Department of Hematology and Hematological Laboratory Science (QZ), Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China (QZ); and Department of Anatomy and Cell Biology (QZ), Rush University Medical Center, Chicago, IL.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Yuting
authors.initials: Y
authors.lastname: Liang
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Haibo
authors.initials: H
authors.lastname: Li
authors.forename: Quanze
authors.initials: Q
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Xue
authors.forename: Cong
authors.initials: C
authors.lastname: Shen
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiang
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Longwei
authors.initials: L
authors.lastname: Qiao
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D024142:Collagen Type VI / Q000235:genetics*; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D016017:Odds Ratio; D010003:Osteoarthritis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011544:Pseudogenes / Q000235:genetics*
chemical_list: C531065:COL6A4P1 protein, human; D024142:Collagen Type VI