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Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
Association between microRNA polymorphisms and the risk of inflammatory bowel disease
Min Zhu1, Diangeng Li2, Meiling Jin2
1Department of Oncology, Division of South Building, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Abstract:
Common single nucleotide polymorphisms (SNPs) in precursor microRNAs may change their properties via altering the expression of miRNAs, resulting in diverse functional consequences. The present study evaluated the effects of four common SNPs in pro-miRNAs on the risk of inflammatory bowel disease (IBD) and IBD‑associated colorectal cancer (IBD-CRC). In a hospital based case‑control investigation in a Chinese population, 468 patients with IBD and 450 age- and gender-matched healthy subjects were enrolled in the present study. The SNPs were genotyped using a polymerase chain reaction (PCR)-restriction fragment length polymorphism technique. The expression levels of the miRNAs were detected by reverse transcription‑PCR. For rs2910164, the risk of IBD was significantly increased in the GC and CC genotypes. The mean expression levels of mir‑146a in the CC and GC genotypes were lower, compared with that of the GG genotype. For rs2292832, an increased risk of IBD was detected in the recessive model of the TT genotype, compared with the combination of the CT and CC genotypes. The [T] allele was found to be at increased significantly, with a 1.268‑fold increased risk of IBD, compared with the [C] allele. The mean expression levele of mir‑149 expression level in the TT genotype was lower, compared with that of the CC genotype. For rs11614913, the risk of IBD‑CRC was significantly increased in the CC genotype, compared with the TT genotype. In the dominant model, the CC genotype had a high risk of IBD‑CRC, compared with the combination of the CT and TT genotypes. These findings suggested that mir-146a rs2910164 and mir‑149 rs2292832 may be associated with the increased risk of IBD via alterations in the expression levels of miRNAs. Therefore, mir‑196a rs11614913 may contribute to the progression of IBD-CRC.
Insights
Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are linked to inflammatory bowel disease (IBD) and IBD-associated colorectal cancer (IBD-CRC). Specific SNPs in mir-146a and mir-149 influence IBD risk by altering miRNA expression, while a mir-196a SNP impacts IBD-CRC progression.
Area of Science:
- Genetics
- Molecular Biology
- Gastroenterology
Background:
- Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes can affect miRNA expression and function.
- These genetic variations may influence susceptibility to complex diseases like inflammatory bowel disease (IBD) and associated cancers.
- Investigating specific miRNA SNPs offers insights into disease pathogenesis.
Purpose of the Study:
- To evaluate the association between common SNPs in precursor miRNAs and the risk of IBD.
- To assess the role of these SNPs in the development of IBD-associated colorectal cancer (IBD-CRC).
- To examine the impact of these SNPs on miRNA expression levels.
Main Methods:
- A hospital-based case-control study involving 468 IBD patients and 450 healthy controls from a Chinese population.
- Genotyping of four common pro-miRNA SNPs using polymerase chain reaction (PCR)-restriction fragment length polymorphism.
- Quantification of miRNA expression levels via reverse transcription-PCR.
Main Results:
- The rs2910164 (mir-146a) SNP was associated with increased IBD risk (GC/CC genotypes) and lower mir-146a expression.
- The rs2292832 (mir-149) SNP showed increased IBD risk (TT genotype, T allele) with reduced mir-149 expression.
- The rs11614913 (mir-196a) SNP was linked to a higher risk of IBD-CRC (CC genotype).
Conclusions:
- The mir-146a rs2910164 and mir-149 rs2292832 SNPs may contribute to IBD risk through altered miRNA expression.
- The mir-196a rs11614913 SNP might play a role in the progression of IBD-associated colorectal cancer.
- These findings highlight the clinical significance of miRNA genetic variations in IBD and IBD-CRC.
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