Departamento de Medicina Genómica, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", México Xochimilco 289, Arenal de Guadalupe, Del. Tlalpan, CP 14389, Mexico City, Mexico.
Servicio de Radiología, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", México Xochimilco 289, Arenal de Guadalupe, Del. Tlalpan, CP 14389, Mexico City, Mexico.
Mol Biol Rep. 2021 Feb;48(2):1549-1557. doi: 10.1007/s11033-021-06207-1. Epub 2021 Feb 15.
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.
miR-146a(miR-146a)是一种炎症反应调节剂,其表达在骨关节炎(OA)中失调;miR-146a 基因的变异可能会影响 OA 的风险。本研究旨在分析墨西哥梅斯蒂索人群中 miR-146a 基因的两个功能变体与原发性膝关节 OA 之间的关联。
方法和结果。进行了病例对照研究,病例定义为年龄≥40 岁、根据 Kellgren-Lawrence 系统患有原发性膝关节 OA 分级≥2 的个体。对照组为无原发性膝关节 OA 且放射学分级<2 的志愿者。TaqMan 等位基因鉴别分析对 rs2910164 和 rs57095329 进行基因分型。计算等位基因和基因型频率以及 Hardy-Weinberg 平衡(HWE)。在共显性、显性和隐性模型下测试遗传关联。进行非条件逻辑回归以估计关联程度。我们纳入了 310 例病例和 379 例对照。尽管 rs2910164 处于 HWE,但在共显性、显性和隐性模型下均无关联。在 OA 分级 2 的女性中,共显性模型发现 CC 基因型与增加的风险之间存在趋势[比值比(95%置信区间)1.6(0.7-3.5)];在 OA 分级 4 的共显性和隐性模型中也发现了相同的趋势[1.8(0.6-5.4)和 2.0(0.7-5.9)]。相反,在 OA 分级 4 的男性中,CC 基因型在共显性和隐性模型中倾向于与较低的风险相关[0.6(0.1-6.0)和 0.5(0.1-5.1)]。结论。我们的结果表明,miR-146a 基因变异与墨西哥梅斯蒂索人群中的原发性膝关节 OA 无显著相关性。