DNA methyltransferase genes polymorphisms are associated with primary knee osteoarthritis: a matched case –control study

AbstractDNA methylation is an epigenetic mechanism involved in the development of primary osteoarthritis (OA). The association between DNA methyltransferases (DNMTs) genes polymorphisms and diseases in which DNA methylation plays a role in their pathogenesis has been described (e.g., cancer); however, its relationship with OA has not been investigated. The aim of this study was to analyze the association betweenDNMT1,DNMT3A, andDNMT3B polymorphisms with radiologic primary knee OA in Mexican mestizo population. A matched case –control study was conducted (ratio, 1:1). Cases included 244 subjects with definite radiographic knee OA (grade ≥ 2). Controls were matched by age and gender and were subjects with no definite radiographic knee OA/normal (grade <  2). TheDNMTs polymorphisms were genotyped by TaqMan allelic discrimination assays. Conditional logistic regression was carried out, and the genetic association was tested under co-dominant, dominant, and recessive inheritance models. Haplotypes forDNMT1 polymorphisms were constructed and their associations were also tested. The CC genotypes of rs2228611 and rs2228612 ofDNMT1 were associated with a lower risk for primary knee OA under a co-dominant and a recessive model [OR (95% CI) 0.4 (0.2 –0.8)/0.5 (0.3–0.8) and 0.3 (0.1–0.8)/0.3 (0.1–0.7), respectively]. The CT haplotype ofDNMT1 polymorphisms was associated with a lower risk [OR (95% CI) 0.71 (0.51 –0.97)]. The CC genotype of rs2424913 ofDNMT3B was ...
Source: Rheumatology International - Category: Rheumatology Source Type: research