PMID- 33553018 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231110 IS - 2251-6581 (Print) IS - 2251-6581 (Electronic) IS - 2251-6581 (Linking) VI - 19 IP - 2 DP - 2020 Dec TI - SNPs in the 3'-untranslated region of SLC30A8 confer risk of type 2 diabetes mellitus in a south-east Iranian population: Evidences from case-control and bioinformatics studies. PG - 979-988 LID - 10.1007/s40200-020-00590-5 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a heterogenic disease with increasing incidence. The SLC30A8 gene encodes an islet zinc transporter (ZnT8), and its variants have been associated with glucose and pro-insulin levels. This study was aimed to examine the effects of a missense variant (rs13266634 C/T), and two 3'UTR variants (rs2466294 C/G and rs2466293 T/C) in SLC30A8 gene on T2DM risk in a south-east Iranian population. METHODS: In this experiment, 450 patients diagnosed with T2DM and 453 healthy subjects from the same geographic area were enrolled. Genotypes were amplified using the ARMS-PCR method. In silico analyses were performed to determine the effects of the variants on the local structure of mRNA, splicing patterns, and potential miRNA-gene interactions as well. RESULTS: Significant differences were noticed between cases and controls regarding the genotypic and allelic distribution of the studied variants. As regards rs2466293 and rs2466294 variants, enhanced risk of T2DM was found under allelic, dominant, recessive, and codominant models (OR > 1). Besides, different genetic models of rs13266634 were associated with decreased risk of T2DM (OR < 1). Bioinformatics analyses indicated that the rs2466293 variant might influence the binding of some miRNAs, while the G-allele of rs2466294 decreased the stability of SLC30A8-mRNA. CONCLUSIONS: In our population, both SNPs in the 3'-untranslated region of SLC30A8 increased the risk of T2DM, while the rs13266634 variant showed a protective association against T2DM susceptibility. Investigating the effects of other variants in this gene or other ZnTs can further indicate such associations in subjects from the same ethnicity. CI - (c) Springer Nature Switzerland AG 2020. FAU - Sargazi, Saman AU - Sargazi S AD - Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. GRID: grid.488433.0. ISNI: 0000 0004 0612 8339 FAU - Heidari Nia, Milad AU - Heidari Nia M AD - Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. GRID: grid.488433.0. ISNI: 0000 0004 0612 8339 FAU - Sargazi, Fariba Mirani AU - Sargazi FM AD - Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. GRID: grid.488433.0. ISNI: 0000 0004 0612 8339 FAU - Sheervalilou, Roghayeh AU - Sheervalilou R AD - Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. GRID: grid.488433.0. ISNI: 0000 0004 0612 8339 FAU - Saravani, Ramin AU - Saravani R AD - Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. GRID: grid.488433.0. ISNI: 0000 0004 0612 8339 AD - Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. GRID: grid.488433.0. ISNI: 0000 0004 0612 8339 FAU - Mirinejad, Shekoufeh AU - Mirinejad S AD - Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. GRID: grid.488433.0. ISNI: 0000 0004 0612 8339 LA - eng PT - Journal Article DEP - 20200721 PL - Switzerland TA - J Diabetes Metab Disord JT - Journal of diabetes and metabolic disorders JID - 101590741 PMC - PMC7843856 OTO - NOTNLM OT - Diabetes mellitus OT - Gene Polymorphism OT - SLC30A8 COIS- Conflict of interestNone declared. EDAT- 2021/02/09 06:00 MHDA- 2021/02/09 06:01 PMCR- 2021/07/21 CRDT- 2021/02/08 05:44 PHST- 2020/05/08 00:00 [received] PHST- 2020/06/26 00:00 [revised] PHST- 2020/07/15 00:00 [accepted] PHST- 2021/02/08 05:44 [entrez] PHST- 2021/02/09 06:00 [pubmed] PHST- 2021/02/09 06:01 [medline] PHST- 2021/07/21 00:00 [pmc-release] AID - 590 [pii] AID - 10.1007/s40200-020-00590-5 [doi] PST - epublish SO - J Diabetes Metab Disord. 2020 Jul 21;19(2):979-988. doi: 10.1007/s40200-020-00590-5. eCollection 2020 Dec.