| Autor: |
Hidalgo, Bertha, Irvin, M. Ryan, Jin Sha, Degui Zhi, Aslibekyan, Stella, Absher, Devin, Tiwari, Hemant K., Kabagambe, Edmond K., Ordovas, Jose M., Arnett, Donna K. |
| Předmět: |
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| Zdroj: |
Diabetes; Feb2014, Vol. 63 Issue 2, p801-807, 7p, 5 Charts, 3 Graphs |
| Abstrakt: |
Known genetic susceptibility loci for type 2 diabetes (T2D) explain only a small proportion of heritable T2D risk. We hypothesize that DNA methylation patterns may contribute to variation in diabetes-related risk factors, and this epigenetic variation across the genome can contribute to the missing heritability in T2D and related metabolic traits. We conducted an epigenome-wide association study for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) among 837 nondiabetic participants in the Genetics of Lipid Lowering Drugs and Diet Network study, divided into discovery (N = 544) and replication (N = 293) stages. Cytosine guanine dinucleotide (CpG) methylation at ~470,000 CpG sites was assayed in CD4+ T cells using the Illumina In nium HumanMethylation 450 Beadchip. We fit a mixed model with the methylation status of each CpG as the dependent variable, adjusting for age, sex, study site, and T-cell purity as fixed-effects and family structure as a random-effect. A Bonferroni corrected P value of 1.1 x 107 was considered significant in the discovery stage. Significant associations were tested in the replication stage using identical models. Methylation of a CpG site in ABCG1 on chromosome 21 was significantly associated with insulin (P =1.83 x 10-7) and HOMA-IR (P = 1.60 x 10-9). Another site in the same gene was significant for HOMA-IR and of borderline significance for insulin (P =1.29 x 10-7 and P = 3.36 x 10-6, respectively). Associations with the top two signals replicated for insulin and HOMA-IR (P = 5.75 x 10-3 and P = 3.35 x 10-2, respectively). Our findings suggest that methylation of a CpG site within ABCG1 is associated with fasting insulin and merits further evaluation as a novel disease risk marker. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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