Are functional variants of the microRNA-146a gene associated with primary knee OA? Evidence in Mexican mestizo population.

MicroRNA-146a (miR-146a) is an inflammatory response regulator whose expression is deregulated in osteoarthritis (OA); variations in the miR-146a gene could affect OA risk. This study aimed to analyze the association between two functional variants of the miR-146a gene and primary knee OA in Mexican mestizo population. Methods and Results. A case-control study was conducted with cases defined as individuals aged ≥ 40 years with primary knee OA grade ≥ 2, according to the Kellgren-Lawrence system. Controls were volunteers with no primary knee OA with radiographic grade < 2. TaqMan allelic discrimination assays genotyped the rs2910164 and rs57095329. Allelic and genotypic frequencies, as well as the Hardy-Weinberg equilibrium (HWE), were calculated. The genetic association was tested under codominant, dominant, and recessive models. Non-conditional logistic regressions were carried out to estimate the association magnitude. We included 310 cases and 379 controls. Despite rs2910164 being in HWE, there was no association under codominant, dominant, and recessive models. In women with OA grade 2, the codominant model found a trend between the CC genotype and increased risk [OR (95% CI) 1.6 (0.7-3.5)]; the same trend was found in OA grade 4 in the codominant and recessive models [1.8 (0.6-5.4) and 2.0 (0.7-5.9)]. Conversely, in men with OA grade 4, the CC genotype tended to be associated with a lower risk in the codominant and recessive models [0.6 (0.1-6.0) and 0.5 (0.1-5.1)]. Conclusion. Our results show that miR-146a gene variants are not significantly associated with primary knee OA in Mexican mestizos.

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

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.

Genetic association analysis of Osteopontin and Matrix Gla Protein genes polymorphisms with primary knee osteoarthritis in Mexican population.

Primary osteoarthritis (OA) is a complex entity in which several loci related to different molecular pathways or classes of molecules are associated with its development as demonstrated through genetic association studies. Genes involved in bone formation and mineralization, such as osteopontin (OPN) and Matrix Gla protein (MGP), could also be related with OA. The aim of this study was to evaluate the association between the genetic variants of OPN and MGP with primary knee osteoarthritis in a Mexican population. A case-control study was conducted in 296 patients with primary knee osteoarthritis and in 354 control subjects. Study groups were assessed radiologically. The rs11730582 of OPN and rs1800802, rs1800801, and rs4236 of MGP were determined by TaqMan allele discrimination assays. The haplotypes of the polymorphisms of MGP were constructed. The association was tested through univariate and multivariate non-conditional logistic regression analyses. The polymorphisms of MGP complied with Hardy-Weinberg (HW) equilibrium. The polymorphisms of OPN and MGP were not significantly associated with primary knee osteoarthritis in the codominant, dominant, and recessive models (p > 0.05). Our study suggests that there are no associations between OPN and MGP polymorphisms with primary knee osteoarthritis in Mexican population.

HHIPL-1 (rs2895811) gene polymorphism is associated with cardiovascular risk factors and cardiometabolic parameters in Mexicans patients with myocardial infarction.

Several studies have reported the role of hedgehog interacting protein-like 1 (HHIPL-1) in different pathologies, including cardiovascular disease. The aim of the present study was to analyze the association of HHIPL-1 (rs2895811) polymorphism with myocardial infarction (MI), cardiometabolic parameters, and traditional cardiovascular risk factors in the Mexican population. The polymorphism was genotyped using a TaqMan assay in 1023 patients with MI and 1105 controls. A similar distribution of the polymorphism was observed between studied groups. However, in patients group, the C allele was associated with a decreased risk of developing hypertriglyceridemia (OR = 0.757, Padditive = 0.030, OR = 0.685, Pdominant = 0.020, OR = 0.691, Pcodominant1 = 0.030), metabolic syndrome (OR = 0.746, Padditive = 0.030, OR = 0.647, Pdominant = 0.005, OR = 0.670, Pheterozygote = 0.015, OR = 0.637, Pcodominant1 = 0.005), and insulin resistance (OR = 0.681, Pdominant = 0.045). The results suggest that HHIPL-1 rs2895811 polymorphism is associated with cardiometabolic parameters in Mexican patients with MI.