DNA Methylation Analysis of the Insulin-like Growth Factor-1 (IGF1) Gene in Swedish Men with Normal Glucose Tolerance and Type 2 DiabetesTianwei Gu1*, Harvest F Gu1,2, Agneta Hilding1, Claes-Göran Östenson1,2 and Kerstin Brismar1,2
- *Corresponding Author:
- Tianwei Gu
M1:03 Rolf Luft Research Center for Diabetes and Endocrinology
Karolinska University Hospital, Stockholm, SE-171 76 Sweden
Tel: +46-(0)8-517 7
E-mail: [email protected]
Received date: June 19, 2014; Accepted date: August 27, 2014; Published date: September 05, 2014
Citation: Gu T, Gu HF, Hilding A, Östenson CG, Brismar K (2014) DNA Methylation Analysis of the Insulin-like Growth Factor-1 (IGF1) Gene in Swedish Men with Normal Glucose Tolerance and Type 2 Diabetes. J Diabetes Metab 5:419 doi: 10.4172/2155-6156.1000419
Copyright: © 2014 Gu T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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<0.001), while serum IGF-I levels were lower in T2D than that in NGT subjects (152 μg/l vs 169 μg/l, P=0.029). In SNP rs35767(C/T), the carriers with CC genotype had higher DNA methylation levels at SNP-CpG site compared with the carriers with CT and TT genotypes in both NGT and T2D.
Conclusions: The present study provides the first evidence that increased DNA methylation levels of the IGF1 gene and decreased serum IGF-I protein concentration are associated with T2D, and suggests that DNA methylation in the IGF1 gene may interact with SNP rs35767 (C/T) in the gene promoter region.