Association of rs2862851 in TGFA Gene with Peripheral TGFA Levels and the Severity of Knee Osteoarthritis in the Han Chinese Population

Osteoarthritis (OA) is a complex joint disorder characterized by sclerosis of subchondral bone. The knee is one of the most commonly affected joints. Given that the genetic mechanisms underlying knee OA remain elusive, our study aims were to first confirm the association of the gene alleles with the risk of knee OA and, second, to evaluate the relationship between peripheral TGFA concentrations and knee OA in an independent Han Chinese population. We performed a case-control study consisting of 392 knee OA patients and 808 unrelated healthy controls. Single-marker-based association analyses and haplotype-based analyses using 3 single nucleotide polymorphisms (SNPs) were performed to confirm the association of gene alleles with the risk of knee OA. Furthermore, we used enzyme-linked immunosorbent assay (ELISA) kits to detect the peripheral blood TGFA concentrations in patients and healthy controls and then evaluated the relationships between the TGFA alleles and genotypes with serum TGFA levels. We replicated the genetic association of the rs2862851 T allele with the risk of knee OA ( = 1.68 × 10 , = 1.41). Moreover, we observed that the peripheral TGFA concentrations were higher in knee OA patients than in healthy controls ( = 8.15 × 10 ). The peripheral TGFA concentrations were significantly different among the various rs2862851 genotypes for both cases ( = 4.16 × 10 ) and controls ( = 7.24 × 10 ). The individuals with the TT genotype in both cases and controls, had the highest peripheral TGFA concentrations. Moreover, with the increase in knee OA grade, peripheral TGFA concentration also increased ( = 1.36 × 10 ). Our study confirmed the association of the gene with the risk of knee OA and identified a positive correlation between peripheral TGFA levels and the severity of knee OA in the Han Chinese population, providing clues for understanding the etiology of knee OA.