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Gene. 2018 Oct 30;675:265-271. doi: 10.1016/j.gene.2018.07.002. Epub 2018 Jul 4.

Genetic variants in long noncoding RNA H19 and MEG3 confer risk of type 2 diabetes in an Iranian population.

Author information

1
Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Urogenital stem cell research center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3
Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
4
Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
5
Department of Nutrition, School of Health, Yasuj University of Medical Sciences, Yasuj, Iran.
6
Department of Laboratory Sciences, Faculty of Paramedicine, Yasuj University of Medical Sciences, Yasuj, Iran. Electronic address: behnam.alipour@yums.ac.ir.

Abstract

PURPOSE:

Long-noncoding RNAs (lncRNAs) have been reported to regulate glucose homeostasis and insulin synthesis and secretion. However, the association of genetic variants of lncRNAs and type 2 diabetes (T2D) has not been evaluated. Therefore, in the present study we investigated the association between H19 rs217727 and H19 rs3741219 variants and MEG3 rs7158663 polymorphism with T2D susceptibility.

MATERIALS AND METHODS:

The study population consists of 969 subjects including 496 T2D patients and 473 non-diabetic age and sex-matched controls. The H19 and MEG3 variants genotyping were performed by PCR-RFLP method.

RESULTS:

Our results revealed that the T allele of rs217727 was more frequent in T2D group compared with controls (P = 0.007, OR = 1.1, 95% CI:1.02-1.18). Moreover, the rs217727-TT genotype was significantly associated with T2D after adjustment for age, BMI and lipid levels (P = 0.041, OR = 1.53, 95% CI: 1.01-2.32). However, no significant difference was detected for allele or genotype frequencies of H19 rs3741219 between T2D and controls (P = 0.71). Furthermore, the findings showed that the AA genotype of MEG3 rs7158663 was associated with significantly increased risks of T2D compared with the GG genotype (P = 0.026, OR = 1.79, 95% CI: 1.07-2.99). The results remained significance after analysis by logistic regression (P = 0.033, Adjusted OR = 1.72, 95% CI: 1.04-2.84). Finally, bioinformatics analysis showed that these SNPs could alter local RNA folding structure and also the miRNA-lncRNA interactions.

CONCLUSIONS:

Our findings provided the evidence of significant association between H19 rs217727-TT and MEG3 rs7158663-AA genotypes with T2D susceptibility.

KEYWORDS:

H19; Long noncoding RNA; MEG3; Polymorphism; Type 2 diabetes

PMID:
29981420
DOI:
10.1016/j.gene.2018.07.002
[Indexed for MEDLINE]

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