背景:2型糖尿病(T2DM)是一种慢性,终身疾病。T2DM的分子机制和病理生理学尚未完全阐明。长非编码RNA转移相关的肺腺癌转录物1(lncRNAMALAT1)的失调被认为是许多疾病中发现的功能障碍的主要促成因素之一。包括内分泌系统。这项研究的目的是研究lncRNAMALAT1单核苷酸多态性(SNP)与中国汉族人群T2DM之间的关系。
方法:我们对三个SNP进行了基因分型(rs3200401C>T,rs619586A>G,MALAT1基因的rs11227209C>G),包括571名T2DM患者和526名对照。采用logistic回归分析不同基因型与2型糖尿病发病风险的关系,结果用比值比(OR)及其95%置信区间(95CI)表示,然后按年龄分层,性别,BMI。两侧P<0.05被认为具有统计学意义。
结果:我们发现rs3200401多态性的CT+TT基因型与中国汉族人群的T2DM风险增加显著相关(OR=1.77;95%CI:1.35-2.33;P调整<0.001)。而MALAT1rs619586AG+GG基因型与T2DM风险降低相关(OR=0.67;95%CI:0.48-0.94;P调整=0.021).随后的分层分析表明,与rs3200401CC基因型相比,CT+TT基因型与男性的T2DM风险增加相关,女性,年龄≥65岁,和BMI≥24亚组(OR=1.68,95%CI:1.10-2.56,P调整=0.016;OR=1.83,95%CI:1.27-2.62,P调整=0.001;OR=1.86,95%CI:1.38-2.52,P调整<0.001;OR=2.13,95%CI:1.45-3.15,P调整<0.001)。单倍型分析显示,T-A-C单倍型的T2DM风险增加1.533倍(95%CI,1.208-1.945,P<0.001),C-G-G与T2DM风险降低相关。rs11227209与T2DM风险无显著相关性(P>0.05)。
结论:结果表明,MALAT1rs619586和rs3200401在中国汉族人群中具有T2DM的易感性,并为未来糖尿病及其并发症的治疗提供了新的遗传靶标。
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; Padjusted < 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; Padjusted = 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, Padjusted = 0.016; OR = 1.83, 95% CI:1.27-2.62, Padjusted = 0.001; OR = 1.86, 95% CI:1.38-2.52, Padjusted < 0.001; OR = 2.13, 95% CI:1.45-3.15, Padjusted < 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).
CONCLUSIONS: 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.