Journal
JOURNAL OF LIPID RESEARCH
Volume 53, Issue 1, Pages 175-184Publisher
ELSEVIER
DOI: 10.1194/jlr.P018952
Keywords
lipids; lipids/oxidation; mitochondria; omega-3 fatty acids; Alaska Native; healthy obesity
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK-74842, R01-DK-074842-02S1]
- National Center for Research Resources (NCRR) [P20-RR-016430, P30-DK-056336]
- U.S. Public Health Service, National Center for Research Resources (NCRR) [RR-03655]
- National Institutes of Health [HL-075675, HL-091333, AT-003545, DK-097307]
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Variants of carnitine palmitoyltransferase 1A (CPT1A), a key hepatic lipid oxidation enzyme, may influence how fatty acid oxidation contributes to obesity and metabolic outcomes. CPT1A is regulated by diet, suggesting interactions between gene variants and diet may influence outcomes. The objective of this study was to test the association of CPT1A variants with body composition and lipids, mediated by consumption of polyunsaturated fatty acids (PUFA). Obesity phenotypes and fasting lipids were measured in a cross-sectional sample of Yup'ik Eskimo individuals (n = 1141) from the Center of Alaska Native Health Research (CANHR) study. Twenty-eight tagging CPT1A SNPs were evaluated with outcomes of interest in regression models accounting for family structure. Several CPT1A polymorphisms were associated with HDL-cholesterol and obesity phenotypes. The P479L (rs80356779) variant was associated with all obesity-related traits and fasting HDL-cholesterol. Interestingly, the association of P479L with HDL-cholesterol was still significant after correcting for body mass index (BMI), percentage body fat (PBF), or waist circumference (WC). Our findings are consistent with the hypothesis that the L479 allele of the CPT1A P479L variant confers a selective advantage that is both cardioprotective (through increased HDL-cholesterol) and associated with reduced adiposity.-Lemas, D.J., H.W. Wiener, D.M. O'Brien, S. Hopkins, K.L. Stanhope, P.J. Havel, D.B. Allison, J.R. Fernandez, H.K. Tiwari, and B.B. Boyer. Genetic polymorphisms in carnitine palmitoyltransferase 1A gene are associated with variation in body composition and fasting lipid traits in Yup'ik Eskimos. J. Lipid Res. 2012. 53: 175-184.
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