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Methylation at CPT1A locus is associated with lipoprotein subfraction profiles
Alexis C Frazier-Wood1, Stella Aslibekyan2, Devin M Absher3
1USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Journal of Lipid Research
|April 9, 2014
Summary
DNA methylation in the CPT1A gene is linked to variations in VLDL and LDL lipoprotein subfractions, offering new insights into cardiometabolic disease risk. This epigenetic factor contributes to metabolic dysfunction beyond genetic influences.
Area of Science:
- Epigenetics
- Metabolic Disease
- Lipidomics
Background:
- Lipoprotein subfractions are key indicators of cardiometabolic disease risk.
- Genetic factors explain only a portion of the variation in lipoprotein measures.
- The role of epigenetics, specifically DNA methylation, in lipoprotein variation is not fully understood.
Purpose of the Study:
- To investigate the association between genome-wide DNA methylation and lipoprotein subfraction measures.
- To identify specific epigenetic markers contributing to interindividual differences in lipoprotein profiles.
Main Methods:
- Genome-wide screening of approximately 470,000 CpG sites for methylation status in CD4(+) T cells from 663 participants (discovery) and 331 participants (replication).
- Linear mixed models were used to assess associations between CpG methylation and 14 lipoprotein subfraction measures, adjusting for covariates.
- Statistical significance was determined using stringent thresholds (P < 1.1 × 10(-7) for discovery, P < .004 for replication).
Main Results:
- Two significant CpG sites within the carnitine palmitoyltransferase-1A (CPT1A) gene were associated with VLDL and LDL subfraction parameters.
- These associations were consistently observed in both discovery and replication cohorts, with a combined P-value of P < 1.1 × 10(-12).
- CPT1A is known to be regulated by PPARα, a target for cardiovascular disease (CVD) drug development.
Conclusions:
- DNA methylation in the CPT1A gene plays a significant epigenetic role in regulating lipoprotein metabolism.
- These findings highlight CPT1A as a potential epigenetic target for understanding and managing metabolic dysfunction and CVD risk.
