Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Graduate Program in Medical Sciences: Endocrinology, Faculty of Medicine, Department of Internal Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Acta Ophthalmol. 2021 Jun;99(4):e461-e469. doi: 10.1111/aos.14638. Epub 2020 Oct 29.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. MiRNA-126 and miRNA-146a have been described as having abnormal expressions in diabetic retinopathy (DR) patients. Polymorphisms in genes codifying miRNAs (miRSNPs) may alter the expression of the corresponding miRNA and, thus, interfere with susceptibility to DR. Therefore, miRSNPs in miR-126 and miR-146a genes could be associated with DR susceptibility. The purpose of this study was to investigate the association between miR-126 rs4636297 (G/A) and miR-146a rs2910164 (G/C) miRSNPs and DR.
This case-control study included 195 type 1 diabetes mellitus (T1DM) patients with DR (cases) and 215 patients without DR and with ≥10 years of T1DM (controls). MiRSNPs were genotyped by real-time PCR.
Genotype distributions of two analysed miRSNPs were in Hardy-Weinberg equilibrium in controls (p > 0.050). Frequencies of the miR-126 rs4636297 miRSNP were not significantly different between case and control groups (p = 0.169). However, after adjustment for age, glycated haemoglobin, triglycerides, estimated glomerular filtration rate and ethnicity, the A allele of this miRSNP was associated with protection for DR under additive [OR: 0.444 (95% CI: 0.211-0.936), p = 0.033] and dominant [OR: 0.512 (95% CI: 0.303-0.865), p = 0.012] inheritance models. Genotype and allele frequencies of miR-146a rs2910164 miRSNP did not differ between groups (p = 0.368 and p = 0.957), and this polymorphism was not associated with DR when assuming different inheritance models.
Our results suggest an association between the A allele of miR-126 rs4636297 miRSNP and protection for DR in a Southern Brazilian population.
微小 RNA(miRNAs)是调节基因表达的小型非编码 RNA。已有研究表明,miRNA-126 和 miRNA-146a 在糖尿病视网膜病变(DR)患者中表达异常。编码 miRNA 的基因(miRSNPs)中的多态性可能改变相应 miRNA 的表达,从而干扰 DR 的易感性。因此,miR-126 和 miR-146a 基因中的 miRSNPs 可能与 DR 易感性相关。本研究旨在探讨 miR-126 rs4636297(G/A)和 miR-146a rs2910164(G/C)miRSNPs 与 DR 之间的关联。
本病例对照研究纳入了 195 例 1 型糖尿病(T1DM)合并 DR(病例)和 215 例无 DR 且 T1DM 病程≥10 年的患者(对照组)。采用实时 PCR 法检测 miRSNPs 基因型。
在对照组中,两种分析的 miRSNPs 基因型分布均符合 Hardy-Weinberg 平衡(p>0.050)。病例组和对照组之间 miR-126 rs4636297 miRSNP 的基因型频率无显著差异(p=0.169)。然而,在校正年龄、糖化血红蛋白、三酰甘油、估算肾小球滤过率和种族后,该 miRSNP 的 A 等位基因与 DR 的保护作用呈相加遗传模式[比值比(OR):0.444(95%可信区间:0.211-0.936),p=0.033]和显性遗传模式[OR:0.512(95%可信区间:0.303-0.865),p=0.012]相关。miR-146a rs2910164 miRSNP 的基因型和等位基因频率在两组间无差异(p=0.368 和 p=0.957),且该多态性在不同遗传模型下与 DR 无关。
本研究结果提示,在巴西南部人群中,miR-126 rs4636297 miRSNP 的 A 等位基因与 DR 的保护作用相关。