Association of tag single nucleotide polymorphisms (SNPs) at lncRNA MALAT1 with type 2 diabetes mellitus susceptibility in the Chinese Han population: A case-control study

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a chronic, lifelong disease. The molecular mechanisms and pathophysiology of T2DM have not yet been fully elucidated. Dysregulation of the long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) is considered one of the main contributing factors of the dysfunction found in many diseases, including those of the endocrine system. The aim of this study was to investigate the association between lncRNA MALAT1 single nucleotide polymorphisms (SNPs) and T2DM in the Chinese Han population.

Methods: We genotyped three SNPs (rs3200401 C > T, rs619586 A > G, rs11227209 C > G) of the MALAT1 gene, including 571 T2DM patients and 526 controls. The association between different genotypes and the risk of T2DM was analyzed using logistic regression, and the results were expressed by odds ratio (OR) and its 95% confidence interval (95%CI), and then stratified by age, sex, and BMI. P < 0.05 on both sides was considered as statistically significant.

Results: We found that the CT + TT genotypes of the rs3200401 polymorphism were significantly associated with an increased risk of T2DM in Chinese Han population (OR = 1.77; 95% CI:1.35-2.33; P_adjusted < 0.001), whereas MALAT1 rs619586 AG + GG genotypes were associated with a reduced risk of T2DM (OR = 0.67; 95% CI:0.48-0.94; P_adjusted = 0.021). Subsequent stratified analysis showed that compared with the rs3200401 CC genotype, CT + TT genotypes were associated with an increased risk of T2DM in the male, female, age ≥ 65 years, and BMI ≥ 24 subgroups (OR = 1.68, 95% CI:1.10-2.56, P_adjusted = 0.016; OR = 1.83, 95% CI:1.27-2.62, P_adjusted = 0.001; OR = 1.86, 95% CI:1.38-2.52, P_adjusted < 0.001; OR = 2.13, 95% CI:1.45-3.15, P_adjusted < 0.001; respectively). Haplotype analysis showed that T-A-C haplotype had a 1.533-fold increased risk of T2DM (95% CI, 1.208-1.945, P < 0.001) and C-G-G was associated with a decreased risk of T2DM. No significant association was found between rs11227209 and T2DM risk (P > 0.05).

Conclusion: The results suggest that MALAT1 rs619586 and rs3200401 confer susceptibility for T2DM in the Chinese Han population and provide new genetic targets for the treatment of diabetes and its complications in the future.

Keywords: Diabetes mellitus; MALAT1; Polymorphism; long non-coding RNA.