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Functional Polymorphism Located in the microRNA Binding Site of the Insulin Receptor (INSR) Gene Confers Risk for Type 2 Diabetes Mellitus in the Bangladeshi Population

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Abstract

Bangladesh has the second largest number of adults with diabetes in South Asia. Compelling evidence suggest that miRNAs contribute to the etiology of Type 2 diabetes mellitus (T2DM) by regulating many aspects of glucose homeostasis. Hence, we hypothesized that genetic polymorphisms in the diabetes-related miRNA target-binding sites could be associated with the risk of T2DM in Bangladesh. The reference Single nucleotide polymorphism (SNP) data from the Insulin Receptor (INSR) gene were downloaded from the ENSEMBL genome browser release 88 and further analyzed in silico for identifying SNPs with deleterious effect and clinical relationships. Further, case–control study using the microRNA-binding site polymorphism rs1366600 (T > C) located at the 3′ UTR of the INSR gene was carried out in 217 T2DM patients and 237 healthy controls from Bangladesh. Genotyping was performed using the real time PCR based allele discrimination method. The results showed that the minor allele ‘C’ is associated with increased risk of T2DM [Odds ratio (OR) 1.87; 95% confidence intervals (CI) 1.28–2.74; P = 0.0010]. When we dissected our analysis to include the dominant model (CC + TC genotype against the TT genotype), we found that the CC and TC genotypes were associated with increased risk of T2DM in Bangladeshi population (OR 2.01; 95% CI 1.31–3.07; P = 0.0012). However, in recessive model (CC vs TT + TC); the effect was not statistically significant (OR 2.23; 95% CI 0.66–7.51; P = 0.1848). Stratification of our data based on the gender of the cases and controls showed similar degree of risk association with respect to different genotypes and alleles. Our study showed that the miRNA binding site polymorphism rs1366600 located at the 3′-UTR region of the INSR gene is associated with increased risk of T2DM in Bangladeshi individuals.

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Acknowledgement

We would like to acknowledge the generosity of the individuals who participated in this study. We would also like to thank Professor Dr Haseena Khan, Department of Biochemistry and Molecular Biology, University of Dhaka for providing us the facilities for performing RT-PCR based allelic discrimination assay.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Correspondence to Md. Ismail Hosen.

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The original version of this article was revised: The co-author name should be Farhana Jahan instead of Farhan Jahan. This has been corrected in this version.

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Parvin, M., Jahan, F., Sarkar, P.K. et al. Functional Polymorphism Located in the microRNA Binding Site of the Insulin Receptor (INSR) Gene Confers Risk for Type 2 Diabetes Mellitus in the Bangladeshi Population. Biochem Genet 57, 20–33 (2019). https://doi.org/10.1007/s10528-018-9872-7

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