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Journal of Lipid Research, Vol. 50, 1223-1228, June 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I

Chandheeb Rajakumar^*, Matthew R. Ban^*, Henian Cao^*, T. Kue Young, Peter Bjerregaard and Robert A. Hegele^1,*

^* Vascular Biology Research Group, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada
National Institute of Public Health, Copenhagen, Denmark

Published, JLR Papers in Press, January 29, 2009.

This work was supported by the Jacob J. Wolfe Distinguished Medical Research Chair, the Edith Schulich Vinet Canada Research Chair (Tier I) in Human Genetics, and operating grants from the Canadian Institutes for Health Research (MOP-13430, MOP-39533, and MOP-39833), the Heart and Stroke Foundation of Ontario (PRG-5967, NA-6059, and T-6018), the Ontario Research Fund, and by Genome Canada through the Ontario Genomics Institute.

¹ To whom correspondence should be addressed. e-mail: hegele{at}robarts.ca

Carnitine palmitoyltransferase IA, encoded by CPT1A, is a key regulator of fatty acid metabolism. Previously, a loss-of-function mutation, namely, c.1436 CT (p.P479L), was reported in CPT1A in the homozygous state in Canadian aboriginal male with presumed CPT1A deficiency. To determine the population frequency of this variant, we determined CPT1A p.P479L genotypes in 1111 Greenland Inuit. Associations between genotype and variation in plasma total cholesterol, triglycerides, LDL, HDL, apolipoprotein (apo) B, and apoA-I was also investigated. We found the L479 allele occurs at a high frequency in this sample (0.73), while it was completely absent in 285 nonaboriginal samples. This suggests that the original proband's symptoms were not likely due to the CPT1A p.P479L mutation because it is very common in Inuit and because symptoms suggesting CPT1A deficiency have not been reported in any carrier subsequently studied. However, CPT1A p.P479L was associated with elevated plasma HDL and apoA-I levels. The association with increased levels of HDL and apoA-I suggest that the polymorphism might protect against atherosclerosis.

Supplementary key words aboriginal • metabolism • genomics • high density lipoprotein • atherosclerosis

Abbreviations: apo, apolipoprotein; CPT1A, carnitine palmitoyltransferase IA; BMI, body mass index; PPAR, peroxisome proliferator-activated receptor ; LPS, lipopolysaccharide

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