Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I.
Carnitine palmitoyltransferase IA, encoded by CPT1A, is a key regulator of fatty acid metabolism. Previously, a loss-of-function mutation, namely, c.1436 C-->T (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.
Rajakumar
Chandheeb
C
Vascular Biology Research Group, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
Ban
Matthew R
MR
Cao
Henian
H
Young
T Kue
TK
Bjerregaard
Peter
P
Hegele
Robert A
RA
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D016632:Apolipoprotein A-I / Q000097:blood*; D050197:Atherosclerosis / Q000097:blood / Q000201:enzymology / Q000517:prevention & control; D001483:Base Sequence; D002334:Carnitine O-Palmitoyltransferase / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006116:Greenland; D006801:Humans; D004930:Inuit / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D017931:DNA Primers; D008074:Lipoproteins; D002334:Carnitine O-Palmitoyltransferase