Epigenetic and Genetic Variations at the TNNT1 Gene Locus are Associated with HDL-C Levels and Coronary Artery Disease

Abstract

Aim: To assess whether epigenetic and genetic variations at the TNNT1 gene locus are associated with high-density lipoprotein cholesterol (HDL-C) and coronary artery disease (CAD). Patients, materials & methods:TNNT1 DNA methylation and c.-20G>A polymorphism were genotyped in subjects with and without familial hypercholesterolemia (FH). Results: Lower TNNT1 DNA methylation levels were independently associated with lower HDL-C levels and with the TNNT1 c.-20G>A polymorphism. In FH men, carriers of the TNNT1 c.-20G>A polymorphism had lower HDL-C levels and an increased risk of CAD compared with noncarriers. In non-FH men, a higher TNNT1 DNA methylation level was associated with CAD. Conclusion: These results suggest that TNNT1 genetic and epigenetic variations are associated with HDL-C levels and CAD.

Keywords::

• 19q13.42
• cardiovascular disease
• DNA methylation
• dyslipidemia
• missing heritability
• SNP
• TNNT1 c.-20G>A polymorphism (rs9636153)

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: http://www.tandfonline.com/doi/full/10.2217/epi.15.120

Acknowledgements

The authors are thankful to all participants and the staff of the ECOGENE-21 Laboratory and Clinical Research Center and the Centre de Recherche de l’IUCPQ biobank. They particularly acknowledge the contribution of S Claveau, N Mior, D Morin, J Landry, C Aubut, C Bélanger, C Racine and N Gaudreault for their dedicated work.

Author contributions

SP Guay contributed to the study design, performed the data collection, the data analysis/interpretation and wrote the manuscript. C Légaré contributed to the data collection, the data analysis/interpretation and the writing of the manuscript. D Brisson conceived the study design, participated in the data analysis/interpretation process and revised the manuscript. P Mathieu and Y Bossé participated in the data collection, analysis and interpretation and revised the manuscript. D Gaudet contributed to the study design, supplied the familial hypercholesterolemia patients’ genotype and clinical evaluation, research infrastructure and revised the manuscript. L Bouchard conceived the study design, participated in the data analysis/interpretation process and revised the manuscript.

Financial & competing interests disclosure

SP Guay was the recipient of a doctoral research award from the Canadian Institutes for Health and Research (CIHR). C Légaré was recipient of three master’s awards from: the Fonds de recherche du Québec – Santé (FRQS), the Corporation de recherche et d’action sur les maladies héréditaire (CORAMH) and the Centre de recherche médicale de l’Université de Sherbrooke. At the time of this study, D Gaudet held the Canada Research Chair in preventive genetics and community genomics. Y Bossé was the recipient of a Junior 2 Research Scholar from the FRQS and now holds a Canada Research Chair in Genomics of Heart and Lung Diseases. P Mathieu is a senior research scholar from the FRQS. L Bouchard is a junior research scholar from the FRQS and a member of the FRQS-funded Centre de recherche clinique du Centre hospitalier universitaire de Sherbrooke (CHUS). This project was supported by ECOGENE-21, the CIHR team in community genetics (Grant #CTP-82941), the Fondation des maladies du coeur du Québec, the FRQS 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

SP Guay was the recipient of a doctoral research award from the Canadian Institutes for Health and Research (CIHR). C Légaré was recipient of three master’s awards from: the Fonds de recherche du Québec – Santé (FRQS), the Corporation de recherche et d’action sur les maladies héréditaire (CORAMH) and the Centre de recherche médicale de l’Université de Sherbrooke. At the time of this study, D Gaudet held the Canada Research Chair in preventive genetics and community genomics. Y Bossé was the recipient of a Junior 2 Research Scholar from the FRQS and now holds a Canada Research Chair in Genomics of Heart and Lung Diseases. P Mathieu is a senior research scholar from the FRQS. L Bouchard is a junior research scholar from the FRQS and a member of the FRQS-funded Centre de recherche clinique du Centre hospitalier universitaire de Sherbrooke (CHUS). This project was supported by ECOGENE-21, the CIHR team in community genetics (Grant #CTP-82941), the Fondation des maladies du coeur du Québec, the FRQS 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.