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

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

doi:10.1371/journal.pone.0173447

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

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

Authors

Raju Ranjha¹, Naresh Kumar Meena¹, Abhiraman Singh¹, Vineet Ahuja², Jaishree Paul¹

Affiliations

¹ School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
² Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

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.

MeSH terms

Adolescent
Adult
Case-Control Studies
Colitis, Ulcerative / genetics*
Female
Genotype
Humans
Male
MicroRNAs / genetics*
Phenotype
Polymorphism, Single Nucleotide
Real-Time Polymerase Chain Reaction
Young Adult

Substances

MIRN196 microRNA, human
MIRN499 microRNA, human
MicroRNAs

Grants and funding

JP acknowledges the financial support received from the Department of Biotechnology, New Delhi through a research grant (No.BT/PR8348/MED/30/1023/2013) and partial support from Department of Science and Technology in the form of DST PURSE Grant II- File No. 6(54)/SLS/JP/DST PURSE/2016-17 to the university. RR received JRF/SRF fellowship from CSIR, New Delhi. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.