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miR-196a-2和miR-499变体与溃疡性结肠炎的关联及其与各自miRNA表达的相关性。

Association of miR-196a-2 and miR-499 variants with ulcerative colitis and their correlation with expression of respective miRNAs.

作者信息

Ranjha Raju, Meena Naresh Kumar, Singh Abhiraman, Ahuja Vineet, Paul Jaishree

机构信息

School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

PLoS One. 2017 Mar 16;12(3):e0173447. doi: 10.1371/journal.pone.0173447. eCollection 2017.

DOI:10.1371/journal.pone.0173447
PMID:28301487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5354276/
Abstract

BACKGROUND AND AIM

MicroRNAs are small non-coding RNAs that play an important role in regulating the gene expression of their target genes. SNP miR-196a-2 rs11614913 and miR-499 rs3746444 are reported to have association with the risk and prognosis of multiple-types of inflammatory diseases including IBD. This study was conducted to show if any association of SNP miR-196a-2rs11614913 and miR-499 rs3746444 exists with ulcerative colitis (UC) patients of north Indian population and how these polymorphisms modulate the expression profile of the respective miRNAs.

METHODS

A total of 638 participants including 197 UC patients and 441 controls were included in this study. Polymorphisms were genotyped by PCR-RFLP and the miRNA expression was measured using qRT-PCR. Genotypes and allele frequencies were calculated using SPSS 16 software.

RESULTS

MiR-196a-2 rs11614913 (C>T) and miR-499 rs3746444 (T>C) were found to be associated with UC. TT genotype of miR-196a-2 rs11614913 (p = 0.03) was negatively associated with UC whereas the heterozygous TC genotype of miR-499 rs3746444 (p = 0.003) was showing positive association with UC. Patients having a combination of both SNPs, developed disease at older age and they suffered from severe disease extent. Genotype that showed association with the disease also showed correlation with the changes in miRNA expression.

CONCLUSION

In this study we found miR-196a-2 rs11614913 and miR-499 rs3746444 were associated with UC in north Indian population. We found the genotype that showed association with UC also altered the expression of respective miRNA in the patient harboring the genotype. There was correlation between associated genotype and altered miRNA expression.

摘要

背景与目的

微小RNA是一类小的非编码RNA,在调节其靶基因的基因表达中发挥重要作用。据报道,单核苷酸多态性(SNP)miR-196a-2 rs11614913和miR-499 rs3746444与包括炎症性肠病(IBD)在内的多种炎症性疾病的风险和预后相关。本研究旨在探讨SNP miR-196a-2 rs11614913和miR-499 rs3746444与北印度人群溃疡性结肠炎(UC)患者是否存在关联,以及这些多态性如何调节各自微小RNA的表达谱。

方法

本研究共纳入638名参与者,其中包括197例UC患者和441名对照。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对多态性进行基因分型,并使用实时定量聚合酶链反应(qRT-PCR)测量微小RNA的表达。使用SPSS 16软件计算基因型和等位基因频率。

结果

发现miR-196a-2 rs11614913(C>T)和miR-499 rs3746444(T>C)与UC相关。miR-196a-2 rs11614913的TT基因型(p = 0.03)与UC呈负相关,而miR-499 rs3746444的杂合TC基因型(p = 0.003)与UC呈正相关。同时具有这两种单核苷酸多态性的患者发病年龄较大,且病情严重程度较高。与疾病相关的基因型也与微小RNA表达的变化相关。

结论

在本研究中,我们发现miR-196a-2 rs11614913和miR-499 rs3746444与北印度人群的UC相关。我们发现与UC相关的基因型也改变了携带该基因型患者中各自微小RNA的表达。相关基因型与微小RNA表达改变之间存在相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c90/5354276/14b134fffbbe/pone.0173447.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c90/5354276/26050b89027c/pone.0173447.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c90/5354276/b38b73a3ad82/pone.0173447.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c90/5354276/c34ef3723057/pone.0173447.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c90/5354276/14b134fffbbe/pone.0173447.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c90/5354276/26050b89027c/pone.0173447.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c90/5354276/b38b73a3ad82/pone.0173447.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c90/5354276/c34ef3723057/pone.0173447.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c90/5354276/14b134fffbbe/pone.0173447.g004.jpg

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