ADRB3 gene promoter DNA methylation in blood and visceral adipose tissue is associated with metabolic disturbances in men

Abstract

Aim: ADRB3 DNA hypermethylation was recently associated with dyslipidemia in familial hypercholesterolemia (FH). In this study, we verified whether ADRB3 DNA methylation in blood and visceral adipose tissue (VAT) was associated with obesity and its related complications. Methods: DNA methylation levels were measured in the blood of 61 FH men, and the blood and VAT of 30 severely obese men. Common ADRB3 polymorphisms were genotyped in all subjects. Results: Higher ADRB3 DNA methylation levels were significantly associated with lower low-density lipoprotein cholesterol levels (r = -0.40; p = 0.01) in FH, and with a lower waist-to-hip ratio (r = -0.55; p = 0.01) and higher blood pressure (r = 0.43; p = 0.05) in severely obese men. ADRB3 g.-843C>T and p.W64R polymorphisms were found to be strongly associated (p < 0.001) with ADRB3 DNA methylation and mRNA levels. Conclusion: Although further studies are needed, these results suggest that epigenetic changes at the ADRB3 gene locus might be involved in the development of obesity and its related metabolic complications.

Keywords::

• ADRB3
• blood lipid profile
• blood pressure
• DNA methylation
• polymorphisms
• waist-to-hip ratio

Acknowledgements

The authors are thankful to all participants and the staff of the ECOGENE-21 Laboratory and Clinical Research Center. They particularly acknowledge the contribution of Sébastien Claveau, Nadia Mior, Denise Morin, Jeannine Landry, Chantale Aubut and Céline Bélanger for their dedicated work, and the contribution of André Tchernof and the bariatric surgeons (Frédéric-Simon Hould, Stéfane Lebel, Picard Marceau and Fady Moustarah) for providing us the blood and VAT samples from the severely obese men.

Supplementary data

Financial & competing interests disclosure

Simon-Pierre Guay was recipient of a doctoral research award from the Canadian Institute for Health and Research (CIHR). Dr Daniel Gaudet held the Canada Research Chair in preventive genetics and community genomics. Luigi Bouchard is a junior research scholar from the Fonds de la recherche en santé du Québec (FRQS) and a member of the FRQ-S funded Centre de recherché Étienne-Le Bel. Marie-Claude Vohl holds the Canada Research Chair in Genomics Applied to Nutrition and Health. Benoit Lamarche holds the Chair in Nutrition and Cardiovascular Health at the Department of Food Sciences and Nutrition of Laval University. This project was supported by the ECOGENE-21 CIHR team in community genetics (grant #CTP-82941), the Fondation des maladies du Coeur du Québec, the FRQ-S and the Banting Research Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate insti­tutional review board approval or have followed the princi­ples outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investi­gations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

Simon-Pierre Guay was recipient of a doctoral research award from the Canadian Institute for Health and Research (CIHR). Dr Daniel Gaudet held the Canada Research Chair in preventive genetics and community genomics. Luigi Bouchard is a junior research scholar from the Fonds de la recherche en santé du Québec (FRQS) and a member of the FRQ-S funded Centre de recherché Étienne-Le Bel. Marie-Claude Vohl holds the Canada Research Chair in Genomics Applied to Nutrition and Health. Benoit Lamarche holds the Chair in Nutrition and Cardiovascular Health at the Department of Food Sciences and Nutrition of Laval University. This project was supported by the ECOGENE-21 CIHR team in community genetics (grant #CTP-82941), the Fondation des maladies du Coeur du Québec, the FRQ-S and the Banting Research Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.