DNA methylation and gene expression of HIF3A : cross-tissue validation and associations with BMI and insulin resistance

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Main, Ailsa MariaCopenhagen University Hospital (author)

DNA methylation and gene expression of HIF3A : cross-tissue validation and associations with BMI and insulin resistance

Article/chapterEnglish2016

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2016-09-02
Springer Science and Business Media LLC,2016

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LIBRIS-ID:oai:lup.lub.lu.se:41a42a5b-fbb0-407c-a795-361e3ae036a0
https://lup.lub.lu.se/record/41a42a5b-fbb0-407c-a795-361e3ae036a0URI
https://doi.org/10.1186/s13148-016-0258-6DOI

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Language:English
Summary in:English

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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 and HIF3A DNA methylation in the blood and SAT from the same individuals, and whether HIF3A 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 the HIF3A promoter was analyzed in the blood and SAT by pyrosequencing, and HIF3A 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 with HIF3A 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 with HIF3A 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 on HIF3A methylation levels in the blood and HIF3A expression levels in skeletal muscle. Conclusions: Our findings are in line with the previously reported link between BMI and DNA methylation of HIF3A in the blood. The tissue-specific results of HIF3A gene expression indicate that SAT is the more functional tissue in which a low expression may adversely affect whole-body insulin sensitivity.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
Epigenetics
Heritability
Insulin sensitivity
Obesity
Type 2 diabetes

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Gillberg, LinnCopenhagen University Hospital,University of Copenhagen(Swepub:lu)med-lge (author)
Jacobsen, Anna LouisaCopenhagen University Hospital (author)
Nilsson, EmmaLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Copenhagen University Hospital(Swepub:lu)geol-eno (author)
Gjesing, Anette PriorUniversity of Copenhagen (author)
Hansen, TorbenUniversity of Copenhagen (author)
Pedersen, OlufUniversity of Copenhagen (author)
Ribel-Madsen, RasmusOdense University Hospital (author)
Vaag, AllanCopenhagen University Hospital(Swepub:lu)med-ava (author)
Copenhagen University HospitalUniversity of Copenhagen (creator_code:org_t)

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In:Clinical Epigenetics: Springer Science and Business Media LLC8:11868-70751868-7083

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