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Background  Knee osteoarthritis (OA) is a complex disease involving both biomechanical and metabolic factors that alter the tissue homeostasis of articular cartilage and subchondral bone. The catabolic activities of extracellular matrix degradation products, especially fibronectin (FN), have been implicated in mediating cartilage degradation. Chondrocytes express several members of the integrin family which can serve as receptors for FN including integrins α5β1, αvβ3, and αvβ5. The purpose of this study was to determine whether polymorphisms in the FN ( FN-1 ) and integrin genes are markers of susceptibility to, or severity of, knee OA in a Han Chinese population.    Methods  Two independent case–control studies were conducted on 928 patients with knee OA and 693 healthy controls. Ten single nucleotide polymorphisms (SNPs) of  FN-1  and the integrin αV gene ( ITGAV ) were detected using the ABI 7500 real-time PCR system.    Results  The AT heterozygote in  FN-1  (rs940739A/T) was found to be significantly associated with knee OA (adjusted OR = 1.44; 95% CI = 1.16–1.80) in both stages of the study.  FN-1  rs6725958C/A and  ITGAV  rs10174098A/G SNPs were only associated with knee OA when both study groups were combined. Stratifying the participants by Kellgren-Lawrence (KL) score identified significant differences in the  FN-1  rs6725958C/A and rs940739 A/T genotypes between patients with grade 4 OA and controls. Haplotype analyses revealed that TGA and TAA were associated with a higher risk of OA, and that TAG conferred a lower risk of knee OA in the combined population.    Conclusions  Our study suggests that the  FN-1  rs940739A/T polymorphism may be an important risk factor of genetic susceptibility to knee OA in the Han Chinese population.

bmc musculoskeletal disorders

An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population: two independent case- control studies