Single Nucleotide Polymorphisms and Osteoarthritis

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.

FOXP3 rs3761548 polymorphism is associated with knee osteoarthritis in a Turkish population

“…Almost 50 SNPs in 50 different genes are reported to be associated with the risk of OA, but none of them were specifically related to OA. In addition, some polymorphisms were specific to ethnic groups and some of them were specific to OA subtypes . To the best of our knowledge this study provides the first data about the relationship between OA and FOXP3 polymorphism, at least for a Turkish population, and it shows that subjects carrying FOXP3 rs3761548 C variant allele are at higher risk for knee OA in codominant, dominant and overdominant genetic models.…”

The roles of cytosolic quality control proteins, SGTA and the BAG6 complex, in disease

“…The normal major allele homozygote was associated with reduced risk to osteoarthritis while the major-minor allele heterozygote contributed to the increased susceptibility, irrespective of anatomical site and gender in the Croatian population. Results from the study indicate that variations in alleles and genotype of BAG6 affect the etiology of osteoarthritis due to dysfunctions in BAG6 protein regulatory roles (Wang et al, 2016).…”

Models to define the stages of articular cartilage degradation in osteoarthritis development

“…Other genetic predisposition to OA development has been described (Tsezou ; Reynard ; Wang et al . ) but it remains largely unknown, however, whether these influence initiation and/or progression specifically.…”