Background: Insulin 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).
Methods: The 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).
Results: Our 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).
Conclusion: Our 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.
Keywords: polymorphisms, T2DM, insulin resistance, Chinese population, microRNA