Global DNA Methylation Is Associated With Insulin Resistance: A Monozygotic Twin Study

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 2; pp. 542 - 546
• Main Authors: JINYING ZHAO, GOLDBERG, Jack, BREMNER, James D, VACCARINO, Viola
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2012
• Subjects: Alu Elements; Biological and medical sciences; Blood pressure; CpG Islands; Diabetes; Diabetes. Impaired glucose tolerance; Disease; DNA; DNA Methylation; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epigenetics; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic testing; Genetics/Genomes/Proteomics/Metabolomics; Genomes; Glucose; Homeostasis; Humans; Hypertension; Insulin resistance; Insulin Resistance - genetics; Leukocytes; Lipids; Measurement; Medical sciences; Mental depression; Methylation; Middle Aged; Post traumatic stress disorder; Twin studies; Twins; Twins, Monozygotic; Endocrinopathy; Target tissue resistance; DNA; Diabetes mellitus; Metabolic diseases; Insulin resistance; Methylation; Monozygotic twin
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db11-1048

Insulin resistance (IR), the hallmark of type 2 diabetes, may be under epigenetic control. This study examines the association between global DNA methylation and IR using 84 monozygotic twin pairs. IR was estimated using homeostasis model assessment (HOMA). Global DNA methylation of Alu repeats in peripheral blood leukocytes was quantified by bisulfite pyrosequencing. The association between global DNA methylation and IR was examined using generalized estimating equation (GEE) and within-twin pair analyses, adjusting for potential confounders. Results show that methylation levels at all four CpG sites were individually associated with IR by GEE (all false discovery rate-adjusted P values≤0.026). A 10% increase in mean Alu methylation was associated with an increase of 4.55 units (95% CI 2.38-6.73) in HOMA. Intrapair difference in IR was significantly associated with intrapair difference in global methylation level. A 10% increase in the difference in mean Alu methylation was associated with an increase of 4.54 units (0.34-8.71; P=0.036) in the difference in HOMA. Confirmation of the results by intrapair analyses suggests that genetic factors do not confound the association between global DNA methylation and IR. Exclusion of twins taking diabetes medication (n=17) did not change our results.