AUTHOR=Wen Zihao , Zou Xiaoqian , Xie Xin , Zheng Shaoling , Chen Xiaojing , Zhu Kehui , Dong Shirui , Liang Jiayu , Huang Xiuxia , Liu Dandan , Wang Yao , Liu Yumei , Wu Jing , Ying Yuting , Liu Kailiang , Lu Congying , Zhang Baohuan , Yang Guang , Jing Chunxia , Nie Lihong 

TITLE=Association of Polymorphisms in miRNA Processing Genes With Type 2 Diabetes Mellitus and Its Vascular Complications in a Southern Chinese Population

JOURNAL=Frontiers in Endocrinology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00461

DOI=10.3389/fendo.2019.00461

ISSN=1664-2392

ABSTRACT=<p><bold>Objective:</bold> To evaluate the potential association between the genetic variants in miRNA processing genes (<italic>RAN, XPO5, DICER1</italic>, and <italic>TARBP2</italic>) and susceptibility to type 2 diabetes mellitus (T2DM) and its vascular complications, as well as to further investigate their interaction with environmental factors in type 2 diabetes.</p><p><bold>Methods:</bold> We conducted a case-control study in genotyping of five polymorphic loci, including <italic>RAN</italic> rs14035, <italic>XPO5</italic> rs11077, <italic>DICER1</italic> rs13078, <italic>DICER1</italic> rs3742330, and <italic>TARBP2</italic> rs784567, in miRNA processing genes to explore the risk factors for T2DM and diabetic vascular complications. Haplotype analyses, interactions of gene-gene and interactions of gene-environment were performed too.</p><p><bold>Results:</bold> We identified a 36% decreased risk of developing T2DM in individuals with the minor A allele in <italic>DICER1</italic> rs13078 (OR: 0.64; 95%CI: 0.42–0.95; <italic>P</italic>: 0.026). The AA haplotype in <italic>DICER1</italic> was also associated with a protective effect on T2DM compared with the AT haplotype (OR: 0.63; 95%CI: 0.42–0.94; <italic>P</italic>-value: 0.023). T2DM patients with the TT+TC genotype at <italic>RAN</italic> rs14035 had a 1.89-fold higher risk of developing macrovascular complications than patients with the CC genotype (OR: 1.89; 95%CI: 1.04–3.45; <italic>P</italic>-value: 0.037). We also identified two three-factor interaction models. One is a three-factor [<italic>DICER1</italic> rs13078, body mass index (BMI), and triglyceride (TG)] interaction model for T2DM (OR: 5.93; 95%CI: 1.25–28.26; <italic>P</italic> = 0.025). Another three-factor [<italic>RAN</italic> rs14035, hypertension (HP), and duration of T2DM (DOD)] interaction model was found for macrovascular complications of T2DM (<italic>OR</italic> = 41.60, 95%CI = 11.75–147.35, <italic>P</italic> &lt; 0.001).</p><p><bold>Conclusion:</bold> Our study provides new evidence that two single nucleotide polymorphisms (SNPs) of the miRNA processing genes, <italic>DICER1</italic> and <italic>RAN</italic>, and their interactions with certain environmental factors might contribute to the risk of T2DM and its vascular complications in the southern Chinese population.</p>