DNA methylation and gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Main, Ailsa; Gillberg, Linn; Jacobsen, Anna; Nilsson, Emma; Gjesing, Anette; Hansen, Torben; Pedersen, Oluf; Ribel-Madsen, Rasmus; Vaag, Allan
• Is Part Of: Clinical epigenetics. Volume 8:Issue 1(2016)
• Page Start: 1
• Page End: 7
• Publication Date: 2016-12
• Subjects: Epigenetics -- Obesity -- Type 2 diabetes -- Heritability -- Insulin sensitivity; Epigenesis -- Periodicals; Genetic regulation -- Periodicals; Human cytogenetics -- Periodicals; Human molecular genetics -- Periodicals; Cancer -- Genetic aspects -- Periodicals; 611.01816
• DOI: 10.1186/s13148-016-0258-6
• Languages: English
• ISSNs: 1868-7075

Abstract

Abstract Background Associations between BMI and DNA methylation of hypoxia-inducible factor 3-alpha (HIF3A ) in both blood cells and subcutaneous adipose tissue (SAT) have been reported. In this study, we investigated associations between BMI andHIF3A DNA methylation in the blood and SAT from the same individuals, and whetherHIF3A gene expression in SAT and skeletal muscle biopsies showed associations with BMI and insulin resistance. Furthermore, we aimed to investigate gender specificity and heritability of these traits. Methods We studied 137 first-degree relatives of type 2 diabetes (T2D) patients from 48 families, from whom we had SAT and muscle biopsies. DNA methylation of four CpG sites in theHIF3A promoter was analyzed in the blood and SAT by pyrosequencing, andHIF3A gene expression was analyzed in SAT and muscle by qPCR. An index of whole-body insulin sensitivity was estimated from oral glucose tolerance tests. Results BMI was associated withHIF3A methylation at one CpG site in the blood, and there was a positive association between the blood and SAT methylation levels at a different CpG site within the individuals. The SAT methylation level did not correlate withHIF3A gene expression. Interestingly, HIF3A expression in SAT, but not in muscle, associated negatively with BMI and whole-body insulin resistance. We found a significant effect of familiality onHIF3A methylation levels in the blood andHIF3A expression levels in skeletal muscle. Conclusions Our findings are in line with the previously reported link between BMI and DNA methylation ofHIF3A in the blood. The tissue-specific results ofHIF3A gene expression indicate that SAT is the more functional tissue in which a low expression may adversely affect whole-body insulin sensitivity.