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

• Authors: Jinying Zhao, University of Oklahoma Health Sciences Center; Jack Goldberg, Veterans Affairs Office of Research & Development; James Bremner, Emory University; Viola Vaccarino, Emory University
• Journal Title: Diabetes
• Volume: Volume 61, Number 2
• Publisher: American Diabetes Association | 2012-02-01, Pages 542-546
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.2337/db11-1048
• Subjects: Health Sciences, Epidemiology; Biology, Biostatistics; Psychology, Behavioral
• Keywords: Science & Technology; Life Sciences & Biomedicine; Endocrinology & Metabolism; ENDOCRINOLOGY & METABOLISM; EPIGENETIC REGULATION; CARDIOVASCULAR-DISEASE; GENOME INSTABILITY; CPG METHYLATION; HYPERTENSION; INHERITANCE; MECHANISMS; PROMOTER; OBESITY; INFLAMMATION

Abstract

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.