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DNA methyltransferase genes polymorphisms are associated with primary knee osteoarthritis: a matched case-control study. | LitMetric

AI Article Synopsis

  • DNA methylation is an important epigenetic mechanism linked to the development of primary osteoarthritis (OA), but the specific relationship between DNA methyltransferases (DNMTs) gene polymorphisms and OA had not been explored before this study.
  • The research involved a matched case-control study of 244 subjects with definite radiographic knee OA, comparing them to matched controls without OA, using genotyping and statistical models to analyze DNMT polymorphisms.
  • Key findings revealed that certain genotypes of DNMT1 (rs2228611 and rs2228612) were associated with a reduced risk of OA, while a specific genotype of DNMT3B (rs2424913) was linked to an increased risk. *

Article Abstract

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.

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http://dx.doi.org/10.1007/s00296-019-04474-7DOI Listing

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