title: Influence of apolipoprotein E genotype on the reliability of the Friedewald formula in the estimation of low-density lipoprotein cholesterol concentrations.
abstract: Lipoprotein data and apolipoprotein (apo) E genotype from 1302 participants, covering a wide range of total plasma cholesterol levels, were used to examine the impact of apo E genotype on the estimation of low-density lipoprotein cholesterol (LDL-C0 concentrations by the Friedewald formula using high-density lipoprotein cholesterol and triglyceride (TG) concentrations as compared with the beta -quantification reference procedure. The results showed that participants with apo E2/E2 genotype had significantly higher very low-density lipoprotein cholesterol (VLDL-C) concentrations and VLDL-C/TG ratio as well as lower LDL-C concentrations than participants with other apo E genotypes. Heterozygous carriers of the epsilon 2 allele had significantly higher VLDL-C than participants with apo E3/E3 and E4/E3 genotypes. The mean absolute error and the mean percentage of bias in calculated LDL-C according to all apo E genotypes, except E2/E2 genotype, were less than 0.16 mmol/L and 4.4%, respectively. Indeed, the mean error and the mean percentage of bias associated with the LDL-C calculated by the Friedewald formula in the apo E2/E2 group were 0.93 mmol/L and 40.6%, respectively. However, participants with the apo E2/E2 genotype and a type III phenotype showed a mean error and a mean percentage of bias reaching 1.53 mmol/L and 63.5%, respectively, whereas E2/E2 participants with a non-type III phenotype had a mean error and a mean percentage of bias of 0.18 mmol/L and 11.0%, respectively. Moreover, 41.9% to 57.1% of the participants had an absolute bias higher than 5% according to the apo E genotype, except for the apo E2/E2 genotypic group where 88.6% of the participants had an absolute bias higher than 5%. Stepwise multiple linear regression analyses revealed that the apo E genotype contributed to 39.0% of the VLDL-C/TG ratio variance, whereas sex, age, and high-density lipoprotein cholesterol explained between 0.5% and 3.2% of the variance. These results indicate that the apo E genotype exerts a significant influence on the estimation of LDL-C concentrations by the Friedewald formula as compared with the beta-quantification.
authors.affiliation: Lipid Research Center, CHUL Research Center, Quebec, Qc, Canada G1V 4G2.
authors.forename: André J
authors.initials: AJ
authors.lastname: Tremblay
authors.forename: Jean
authors.initials: J
authors.lastname: Bergeron
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gagné
authors.forename: Claude
authors.initials: C
authors.lastname: Gagné
authors.forename: Patrick
authors.initials: P
authors.lastname: Couture
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D002624:Chemistry, Clinical / Q000379:methods / Q000592:standards*; D002648:Child; D002675:Child, Preschool; D008078:Cholesterol, LDL / Q000097:blood*; D015243:Cholesterol, VLDL / Q000097:blood; D005260:Female; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D014280:Triglycerides