DNA Methylation Analysis of the Insulin-like Growth Factor-1 (IGF1) Gene in Swedish Men with Normal Glucose Tolerance and Type 2 Diabetes

Objective: Recent genetic studies have demonstrated that Single Nucleotide Polymorphism (SNP) rs35767(C/T) in the IGF1 gene promoter is associated with insulin resistance and serum IGF-I levels and thereby implicated that IGF1 has genetic effect in Type 2 Diabetes (T2D). The present study aimed to investigate the alteration of DNA methylation levels of the IGF1 gene in T2D. Subjects and methods: A total of 688 Swedish men with Normal Glucose Tolerance (NGT) or T2D were selected from Stockholm Diabetes Prevention Program. DNA methylation levels at rs35767 SNP-CpG site and other three CpG sites (P1-P3) in the IGF1 gene promoter region were analyzed with PyroMark Assays and bisulfite pyrosequencing. Fasting serum IGF-I levels were measured with an in-house radio-immunoassay. Results: DNA methylation levels at CpG site P3 of the IGF1 gene promoter were increased in T2D patients compared with NGT subjects (84.8% vs. 74.2%, P