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From the Department of Medicine, St Michael's Hospital (R.A.H., P.W.C., F.S.), and Samuel Lunenfeld Research Institute and Mount Sinai Hospital, University of Toronto (A.J.G.H., B.Z.), Toronto, Canada; and Thames Valley Family Practice Research Unit, University of Western Ontario (S.B.H.), London, Canada.
Correspondence to Robert A. Hegele, MD, DNA Research Laboratory, St Michael's Hospital, 30 Bond St, Toronto, Ontario, M5B 1W8, Canada. E-mail robert.hegele{at}utoronto.ca
Abstract We hypothesized that common genomic variants would be associated with variation in lipoprotein phenotypes in young subjects. We determined genotypes of FABP2, PON, APOC3, and APOE in 188 aboriginal Canadians, aged 9 to 17 years. We found that 13 of 32 possible genotype-phenotype associations were significant: (1) the FABP2 codon 54 genotype was associated with variation in plasma triglycerides (P=.045); (2) the PON codon 192 genotype was associated with variation in plasma total and LDL cholesterol and apoB (P=.0099, P=.0088, and P=.016, respectively); (3) the APOC3 insulin-response-element genotype was associated with variation in plasma triglycerides, HDL cholesterol, apoA-I, the total cholesterol to HDL cholesterol ratio, and the apoB to apoA-I ratio (P=.0014, P=.0069, P=.045, P=.0021, and P=.0081, respectively); and (4) the APOE restriction isotype was associated with variation in plasma LDL cholesterol, apoB, the total cholesterol to HDL cholesterol ratio, and the apoB to apoA-I ratio (P=.025, P=.034, P=.045, and P=.047, respectively). The average young age and relative absence of age-dependent secondary environmental factors could have eased the identification of small genetic effects on lipoprotein phenotypes in this study sample.
Key Words: apolipoproteins fatty acidbinding protein hyperlipidemia paraoxonase small effects polygenic traits
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