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微小RNA-146a(rs2910164)基因多态性及其对炎症性肠病患者循环微小RNA-146a水平的影响

MiR-146a (rs2910164) Gene Polymorphism and Its Impact on Circulating MiR-146a Levels in Patients with Inflammatory Bowel Diseases.

作者信息

Ghorab Rasha Ahmed, Fouad Shaimaa H, Sherief Ahmed F, El-Sehsah Eman M, Shamloul Sara, Taha Sara I

机构信息

Department of Clinical Pathology, Faculty of Medicine, Ain-Shams University, 11591 Abbasia, Cairo, Egypt.

Department of Internal Medicine /Allergy and Clinical Immunology, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.

出版信息

Inflammation. 2024 Aug 6. doi: 10.1007/s10753-024-02108-0.

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

微小RNA - 146a(miR - 146a)参与了炎症性肠病(IBD)的病理生理过程。然而,具体过程仍未完全明确。相互矛盾的研究表明,miR - 146a rs2910164 C>G多态性可能会影响miR - 146a的表达。这项病例对照研究旨在调查埃及IBD患者中miR - 146a rs2910164 C>G基因多态性及其与循环miR - 146a表达水平的关系。我们纳入了40例IBD患者和30例匹配的健康对照。对所有参与者采用定量实时PCR进行miR - 146a rs2910164多态性基因分型及miR - 146a表达水平评估。在IBD患者组中,分别有47%和70%的患者报告有miR - 146a rs2910164 GG基因型和G等位基因。它们与IBD风险增加相关。所有CC基因型的IBD患者(100%)和大多数CG基因型的患者(66.67%)病情处于非活动期,而大多数GG基因型的IBD患者(73.68%)病情处于活动期。miR - 146a表达水平在CC基因型时最高,在GG基因型时最低。此外,IBD患者的miR - 146a表达水平显著低于对照组,且与疾病活动度相关。联合检测粪便钙卫蛋白和miR - 146a表达水平可提高区分活动期IBD患者和非活动期患者的诊断敏感性和阴性预测值。我们的研究发现,在埃及人群中,miR - 146a rs2910164 GG基因型和G等位基因与IBD易感性增加及疾病活动度密切相关。miR - 146a rs2910164多态性也可降低这些患者的miR - 146a表达水平。对更大样本量和不同种族人群进行进一步研究可能是确立这种基因关联的关键。

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