DNA methyltransferase genes polymorphisms are associated with primary knee osteoarthritis: a matched case–control study
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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.
KeywordsKnee osteoarthritis DNA (cytosine-5-)-methyltransferase Genetic polymorphism Risk factors Matched case–control study Genetic association study
The authors wish to thanks to the personnel of the Radiology Service for the invaluable support to assess the radiologic studies.
Concept, study design, data analysis, manuscript preparation, and writing: Antonio Miranda-Duarte, Verónica Marusa Brogonio-Cuadra, and Norma Celia González-Huerta; Data acquisition (study subject recruitment, clinical and radiologic evaluation, laboratory procedures): Verónica Marusa Brogonio-Cuadra, Norma Celia González-Huerta, Juan Francisco Ahumada-Pérez, Matvey Sosa-Arellano, Emma Xochitl Rojas-Toledo, Eugenio Morales-Hernández, Nonanzit Pérez-Hernández, and José Manuel Rodríguez-Pérez. Acceptance of the final manuscript version: All of the authors.
This work was financially supported by Grant no. 180720 of the Consejo Nacional de Ciencia y Tecnología (CONACyT- México).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics and Investigation Committee of the National Rehabilitation Institute “Luis Guillermo Ibarra Ibarra” and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Approval reference number 13/13 (04/25/2013).
Informed consent was obtained from all individual participants included in the study.
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