Association of ADAMTS-5 gene polymorphisms with the susceptibility to knee osteoarthritis in a Chinese Han population

Osteoarthritis (OA) is the most prevalent type of arthritis and the main reason for progressive disability in middle-aged and older people. Studies of candidate genes may provide a novel insight and treatment strategy for knee osteoarthritis (KOA). The aim of this study was to investigate the relationship between KOA susceptibility and single-nucleotide polymorphism (SNP) of the ADAMTS-5 gene.

The case group included 188 patients from Luoyang Orthopedic Hospital with clinically and radiographically diagnosed primary KOA, and the control group included 100 age-matched individuals without KOA. Fifteen ADAMTS-5 SNPs were assayed using MALDI-TOF MS. Allelic and haplotypic frequencies were compared between the groups. The relationship between genotype distribution and risk of KOA was analyzed by multivariate logistic regression.

The frequency of A allele in rs2249350 site in the KOA group was significantly lower (odds ratio [OR]: 0.761; 95% confidence interval [95% CI]: 0.612-0.947; P = 0.016), while that of C allele was higher than that in the control group (OR: 1.176; 95% CI: 1.025-1.351; P = 0.016). AA genotype and gene model, especially recessive gene model at rs2249350 locus, negatively correlated with KOA risk after adjustment for sex, body mass index, age, and occupation (AA vs. CC: OR: 0.288; 95% CI: 0.124-0.669; P = 0.004; AA vs. CA + CC: OR: 0.348; 95% CI: 0.162-0.749; P = 0.007). Meanwhile, one protective haplotype, GA (rs229054, rs2249350) (OR: 0.763; 95% CI: 0.614-0.949; P = 0.017), and one high-risk haplotype, GC (rs229054, rs2249350) (OR: 1.259; 95% CI: 1.032-1.537; P = 0.019), were found in this study.

Despite a limited sample size, our study suggests that the rs2249350 polymorphism in the ADAMTS-5 gene is one of the genetic factors influencing the risk of KOA. The A allele and AA genotype of rs2249350 may protect from KOA, whereas C allele and CC genotype increase the risk of KOA. In addition, the GA haplotype (rs229054, rs2249350) might be associated with a decreased risk of KOA, whereas the GC haplotype (rs229054, rs2249350) may be a risk factor for KOA. Additional larger-sized studies in more ethnically diverse populations are needed to confirm these findings.