Abstract:
MicroRNA-146a (miR-146a) has been involved in the pathophysiology of inflammatory bowel disease (IBD). However, the precise processes are still not entirely understood. Contradictory studies suggest that miR-146a expression could be influenced by the miR-146a rs2910164 C > G polymorphism. This case-control study aimed to investigate the association of miR-146a rs2910164 C > G gene polymorphism and its impact on circulating miR-146a expression levels in Egyptian IBD patients. We included 40 IBD patients and 30 matched healthy controls. Genotyping of miR-146a rs2910164 polymorphism and assessment of miR-146a expression level were done using quantitative real-time PCR in all participants. MiR-146a rs2910164 GG genotype and the G allele were reported in 47% and 70% of the IBD patient group, respectively. And they were associated with increased IBD risk. All the IBD patients with the CC genotype (100%) and most of those with the CG genotype (66.67%) had an inactive disease, while most IBD patients with the GG genotype (73.68%) had an active disease. The miR-146a expression level was the highest with the CC genotype and the lowest with the GG genotype. Also, miR-146a expression level decreased significantly in IBD patients than controls and with disease activity. Combined detection of fecal calprotectin with miR-146a expression level improved the diagnostic sensitivity and the negative predictive value in differentiating IBD patients with active disease from those inactive. Our study identified a strong association of miR-146a rs2910164 GG genotype and G allele with IBD-increased susceptibility and activity in the Egyptian population. The miR-146a rs2910164 polymorphism can reduce miR-146a expression levels in these patients as well. Further research on a larger sample size and different ethnic populations can be the key to progress in establishing this genetic association.
摘要:
MicroRNA-146a(miR-146a)已参与炎症性肠病(IBD)的病理生理学。然而,确切的过程仍然没有完全理解。矛盾的研究表明miR-146a的表达可能受miR-146ars2910164C>G多态性的影响。本病例对照研究旨在探讨miR-146ars2910164C>G基因多态性的相关性及其对埃及IBD患者循环miR-146a表达水平的影响。我们包括40名IBD患者和30名匹配的健康对照。使用定量实时PCR对所有参与者进行miR-146ars2910164多态性的基因分型和miR-146a表达水平的评估。MiR-146ars2910164GG基因型和G等位基因在47%和70%的IBD患者组中报告,分别。它们与IBD风险增加有关。所有CC基因型(100%)的IBD患者和大多数CG基因型(66.67%)的IBD患者均患有非活动性疾病,而大多数GG基因型的IBD患者(73.68%)患有活动性疾病。miR-146a表达水平在CC基因型中最高,在GG基因型中最低。此外,miR-146a在IBD患者中的表达水平比对照组和疾病活动显著降低。粪便钙卫蛋白与miR-146a表达水平的联合检测提高了区分患有活动性疾病的IBD患者和非活动性疾病的诊断灵敏度和阴性预测值。我们的研究发现,在埃及人群中,miR-146ars2910164GG基因型和G等位基因与IBD易感性和活性增加密切相关。miR-146ars2910164多态性也可以降低这些患者的miR-146a表达水平。对更大样本量和不同种族人群的进一步研究可能是建立这种遗传关联的关键。