1. Department of Endocrinology and Metabolism, The Second People's Hospital of Yunnan Province & The Affiliated Hospital of Yunnan University, Kunming 650021, Yunnan, China.
2. Dali University, Dali 671000, Yunnan, China.
3. Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, Yunnan, China.
4. Department of Medicine, Dentistry and Healthy Science, The University of Melbourne, Melbourne VIC3010, Australia.
*These authors contributed equally to this work.
Background: Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder triggered by insulin resistance in peripheral tissues. Evidence has shown that lipid metabolism and related genetic factors lead to insulin resistance. Hence, it is meaningful to investigate the association between single-nucleotide polymorphisms (SNPs) in lipid metabolism-related genes and T2DM.
Methods: A total of 1,194 subjects with T2DM and 1,274 Non-diabetic subjects (NDM) were enrolled. Five SNPs in three genes (rs864745 in JAZF1, rs35767 in IGF1, and rs4376068, rs4402960, and rs6769511 in IGF2BP2) that contribute to insulin resistance involving lipid metabolism were genotyped using the MassArray method in a Chinese population.
Results: The allele and genotypes of rs6769511 in IGF2BP2 were associated with T2DM (P=0.009 and P=0.002, respectively). In inheritance model analysis, compared with the T/T-C/T genotype, the C/C genotype of rs6769511 in IGF2BP2 was a risk factor for the development of T2DM (P<0.001, odds ratio [OR] =1.76; 95% confidence interval [CI]: 1.29-2.42). Haplotype analysis revealed associations of the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 with the development of T2DM (P=0.015). Additionally, rs4376068C-rs4402960T-rs6769511C was a risk haplotype for T2DM (OR=1.179; 95% CI: 1.033-1.346).
Conclusion: The rs6769511 in IGF2BP2 was associated with T2DM susceptibility, and the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 was associated with the development of T2DM in a Chinese population.
Keywords: Polymorphisms, Chinese population, lipid metabolism-related genes, T2DM