DNA 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 between DNMT1, DNMT3A, and DNMT3B 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). The DNMTs 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 for DNMT1 polymorphisms were constructed and their associations were also tested. The CC genotypes of rs2228611 and rs2228612 of DNMT1 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 of DNMT1 polymorphisms was associated with a lower risk [OR (95% CI) 0.71 (0.51-0.97)]. The CC genotype of rs2424913 of DNMT3B was associated with an increased risk under a co-dominant and a dominant model [OR (95% CI) 3.0 (1.1-8.0), and 1.6 (1.1-2.4), respectively]. Our results show that DNMTs polymorphisms are associated with primary knee OA.

中文翻译：

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DNA甲基转移酶基因多态性与原发性膝骨关节炎相关：一项匹配的病例对照研究。

DNA甲基化是参与原发性骨关节炎（OA）发展的表观遗传机制。已经描述了DNA甲基转移酶（DNMT）基因多态性与DNA甲基化在其发病机理中起作用的疾病之间的关联（例如，癌症）；但是，它与OA的关系尚未得到研究。这项研究的目的是分析墨西哥混血儿人群中DNMT1，DNMT3A和DNMT3B多态性与放射原发性膝骨OA之间的关系。进行了匹配的病例对照研究（比例为1：1）。病例包括244名明确的X线膝骨OA（≥2级）受试者。对照按年龄和性别进行匹配，并且受试者无明确的X线膝骨OA /正常（等级<2）。通过TaqMan等位基因鉴别分析对DNMTs多态性进行基因分型。进行了条件逻辑回归，并在共显性，显性和隐性遗传模型下测试了遗传关联。构建了DNMT1多态性的单倍型，并测试了它们的关联。DNMT1的rs2228611和rs2228612的CC基因型与共显性和隐性模型[OR（95％CI）0.4（0.2-0.8）/0.5（0.3-0.8）和0.3 （0.1-0.8）/0.3（0.1-0.7）]。DNMT1基因多态性的CT单倍型与较低的风险相关[OR（95％CI）0.71（0.51-0.97）]。DNMT3B rs2424913的CC基因型与共显性和显性模型下的风险增加相关[分别为OR（95％CI）3.0（1.1-8.0）和1.6（1.1-2.4）]。我们的结果表明，DNMTs多态性与原发性膝骨关节炎相关。