Sargazi Saman, Heidari Nia Milad, Sargazi Fariba Mirani, Sheervalilou Roghayeh, Saravani Ramin, Mirinejad Shekoufeh
Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
J Diabetes Metab Disord. 2020 Jul 21;19(2):979-988. doi: 10.1007/s40200-020-00590-5. eCollection 2020 Dec.
Type 2 diabetes mellitus (T2DM) is a heterogenic disease with increasing incidence. The 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 gene on T2DM risk in a south-east Iranian population.
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. 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.
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
In our population, both SNPs in the 3'-untranslated region of 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.
2型糖尿病（T2DM）是一种发病率不断上升的异质性疾病。该基因编码一种胰岛锌转运体（ZnT8），其变体与血糖和胰岛素原水平相关。本研究旨在探讨该基因中的一个错义变体（rs13266634 C/T）以及两个3'UTR变体（rs2466294 C/G和rs2466293 T/C）对伊朗东南部人群T2DM风险的影响。
在本实验中，纳入了450例诊断为T2DM的患者和来自同一地理区域的453名健康受试者。使用ARMS-PCR方法扩增基因型。进行分析以确定这些变体对mRNA局部结构、剪接模式以及潜在的miRNA-基因相互作用的影响。
在研究变体的基因型和等位基因分布方面，病例组和对照组之间存在显著差异。对于rs2466293和rs2466294变体，在等位基因、显性、隐性和共显性模型下发现T2DM风险增加（OR>1）。此外，rs13266634的不同遗传模型与T2DM风险降低相关（OR<1）。生物信息学分析表明，rs2466293变体可能影响某些miRNA的结合，而rs2466294的G等位基因降低了稳定性。
在我们的人群中，该基因3'-非翻译区的两个单核苷酸多态性均增加了T2DM的风险，而rs13266634变体显示出对T2DM易感性的保护关联。研究该基因或其他ZnT中的其他变体的影响可以进一步表明同一民族受试者中的此类关联。
