Dataset Information

Association of single nucleotide polymorphisms of miRNAs involved in the GLUT4 pathway in T2DM in a Chinese population.

ABSTRACT: BACKGROUND:The insulin/insulin receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/GLUT4 pathway plays a crucial role in insulin resistance and is closely associated with T2DM. Accumulating evidence indicates that miRNAs (such as miR-135a, let-7d, miR-107, miR-96, miR-29a, miR-23a, miR-126, miR-133a, and miR-106b) influence the GLUT4 pathway. METHODS:A total of 784 subjects with T2DM and 846 nondiabetic subjects were enrolled and 12 single nucleotide polymorphisms (SNPs) in miRNAs (rs10459194 in miR-135a-2, rs10993081 and rs7045890 in let-7d, rs2296616 in miR-107, rs2402959 and rs6965643 in miR-96, rs24168 in miR-29a, rs3745453 in miR-23a, rs4636297 in miR-126, rs8089787 and rs9948906 in miR-133a-1 and rs999885 in miR-106b) involved in the GLUT4 pathway were genotyped using the MassArray method in a Chinese population. RESULTS:Our data showed that the A allele of rs2402959 in miR-96 may increase the risk of developing T2DM (p = .002, OR = 1.266; 95% CI: 1.089-1.471). The genotypes of rs3745453 in miR-23a showed the difference between T2DM and control groups (p < .001). Moreover, for rs2402959, compared with the A/A genotype, the (G/A-G/G) genotype shows a protective effect in T2DM (p = .001, OR = 0.71; 95% CI: 0.58-0.87). For rs3745453, compared with the (A/A-A/G) genotype, the G/G genotype increases the risk of T2DM (p < .001, OR = 1.95; 95% CI: 1.38-2.77). In addition, we also found that rs4636297G/G genotype was associated with lower TC in T2DM group. CONCLUSION:Our results revealed that genetic variations in the miRNAs involved in the GLUT4 pathway were associated with T2DM susceptibility in a Chinese population, and these results emphasize the need to study the functional effects of these variations in the miRNAs involved in the GLUT4 pathway on the risk of developing T2DM.

SUBMITTER: Li Y

PROVIDER: S-EPMC6732275 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Association of single nucleotide polymorphisms of miRNAs involved in the GLUT4 pathway in T2DM in a Chinese population.

Li Yiping Y Li Chuanyin C Yang Man M Shi Li L Tao Wenyu W Shen Keyu K Li Xianli X Wang Xiaoling X Yang Ying Y Yao Yufeng Y

Molecular genetics & genomic medicine 20190807 9

<h4>Background</h4>The insulin/insulin receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/GLUT4 pathway plays a crucial role in insulin resistance and is closely associated with T2DM. Accumulating evidence indicates that miRNAs (such as miR-135a, let-7d, miR-107, miR-96, miR-29a, miR-23a, miR-126, miR-133a, and miR-106b) influence the GLUT4 pathway.<h4>Methods</h4>A total of 784 subjects with T2DM and 846 nondiabetic subjects were enrolled and 12 single nucleoti ...[more]

PMID: 31389668

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Project description:BackgroundInsulin receptor (INSR), insulin receptor substrate (IRS) and glucose transporter 4 (GLUT4) play important roles in the insulin resistance pathway. The microRNA (miRNA or miR) involved in INSR, IRS or GLUT4 could be associated with the development of type 2 diabetes (T2DM).MethodsThe aim of this study was to investigate the association of T2DM with 12 single nucleotide polymorphisms (SNPs) in 7 miRNAs (miR-195, miR-126, miR-144, miR-155, miR-21, miR-93 and miR-222) involved in the insulin resistance pathway. A total of 1593 subjects with T2DM and 1656 nondiabetic subjects were genotyped. Then, the associations of these SNPs with the development of T2DM and individual metabolic traits were evaluated, such as fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1C).ResultsOur data showed that the C allele of rs1292037 in miR-21 could increase the risk of developing T2DM (P = 0.002, OR = 1.17; 95% CI: 1.06-1.29). In addition, the T allele of rs13137 in miR-21 could be a risk factor for T2DM (P = 0.003, OR = 1.16; 95% CI: 1.05-1.28). According to inheritance mode analysis, compared with the T/T-T/C genotype, the C/C genotype of rs1292037 showed a risk effect in T2DM in the recessive mode (P = 0.001, OR = 1.35; 95% CI: 1.13-1.63). For rs13137, compared with the A/A-A/T genotype, the T/T genotype also showed a risk effect in T2DM in the recessive mode (P = 0.001, OR = 1.35; 95% CI: 1.13-1.62). Moreover, in the nondiabetic group, compared with the rs78312845 A/G (FPG = 5.177±0.488mmol/L; HbA1C = 5.147±0.293%) and A/A genotypes (FPG = 5.155±0.486mmol/L; HbA1C = 5.136±0.299%), the G/G genotype (FPG = 4.887±0.482mmol/L; HbA1C = 4.960±0.397%) was associated with lower FPG (P = 0.012 and 0.019) and HbA1C (P = 0.008 and 0.011).ConclusionOur results revealed that rs1292037 and rs13137 in miR-21 were associated with T2DM susceptibility in a Han Chinese population. Moreover, the rs78312845 in miR-195 contributed to the level of FPG and HbA1C in nondiabetic group in the Han Chinese population.

Dataset Information

Association of single nucleotide polymorphisms of miRNAs involved in the GLUT4 pathway in T2DM in a Chinese population.

Publications

Association of single nucleotide polymorphisms of miRNAs involved in the GLUT4 pathway in T2DM in a Chinese population.

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