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Genetic Variants of Pre-microRNAs A-499G(rs3746444) and T-196a2C(rs11614913) with Ulcerative Colitis (UC) and Investigated with Thiopurine-S-Methyltransferase (TPMT) Activity.

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BACKGROUND Abnormal expression and different splicing of miRNAs are involved in several human inflammatory disorders. It has been suggested that gene variants of miRNAs may be associated with increased risk… Click to show full abstract

BACKGROUND Abnormal expression and different splicing of miRNAs are involved in several human inflammatory disorders. It has been suggested that gene variants of miRNAs may be associated with increased risk of ulcerative colitis (UC). We aimed to evaluate the association of two SNPs (miRNA-A-499G(rs3746444) and miRNA-T196a2C(rs11614913)) with the risk of UC and monitor their effect on thiopurine-S-methyltransferase (TPMT) activity in Kurdish population of Iran. METHODS This case-control study was performed on 210 UC patients and 212 healthy individuals. Genotyping assay was performed using PCR-RFLP and the TPMT-activity was measured via non-extraction-HPLC method. RESULTS We found that the existence of GG genotypes and G allele of miRNA-A-499G SNPs significantly increased the risk of UC by 1.76 and 1.32 times, respectively. The distribution of GG genotype (23.8% vs. 16%, χ2 = 4.2, p = 0.041) and G allele (46.4% vs. 39.4%, χ2 = 4, p = 0.046) of miRNA-A-499G, were significantly higher in UC patients compared to control group. Our results indicate that miRNA SNPs (miRNA-T-196a2C and miRNA-A-499G) have no significant effect on TPMT activity of studied population. CONCLUSIONS Our results, for the first time, demonstrate that the GG genotype and G allele of miRNA-A-499G significantly increase the risk of UC. However, miRNA SNPs showed no significant effect on TPMT activity in studied population.

Keywords: 499g rs3746444; mirna 499g; tpmt; tpmt activity; ulcerative colitis

Journal Title: Clinical laboratory
Year Published: 2017

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