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

• Published in: Journal of Lipid Research
• Main Authors: Rajakumar, Chandheeb, Ban, Matthew R, Cao, Henian, Young, T Kue, Bjerregaard, Peter, Hegele, Robert A
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2009
• Subjects: Greenland; inuit
• Online Access: https://portal.findresearcher.sdu.dk/da/publications/8c736b10-2e71-11de-b0ce-000ea68e967b; https://doi.org/10.1194/jlr.P900001-JLR200

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. In order 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 apo A-I were also investigated. We found the L479 allele occurs at a high frequency in this sample (0.73), while it was completely absent in 285 non-aboriginal samples. This suggests the original proband's symptoms were not likely due to the CPT1A p.P479L mutation, since it very common in Inuit and since symptoms suggesting CPT1A deficiency have not been reported in any carrier subsequently studied. However, CPT1A p.P479L was associated with elevated plasma HDL and apo A-I levels. The association with increased levels of HDL and apo A-I suggest that the polymorphism might protect against atherosclerosis.