Polymorphisms in the apolipoprotein (apo) AI-CIII-AIV gene cluster: detection of genetic variation determining plasma apo AI, apo CIII and apo AIV concentrations.
We have examined the associations between levels of plasma apolipoprotein (apo) AI, apo CIII and apo AIV and genetic variation in the apo AI-CIII-AIV gene cluster in 162 boys and young men from Belgium aged from 7 to 23 years. Genotypes were determined for six restriction enzymes XmnI, PstI, SstI, PvuIIA-CIII, PvuIIB-AIV and XbaI, and for the G to A substitution at -75 bp in the 5' region of the apo AI gene. The polymorphism most strongly associated with apo AI levels was the G to A substitution (P = 0.025, R2 x 100 = 3.6%) confirming previous observations. The polymorphism most strongly associated with apo CIII levels was that of PvuIIA-CIII (P = 0.023, R2 x 100 = 2.9%) in the apo CIII gene. This novel association must be interpreted with caution until it has been confirmed in an independent sample. The polymorphism associated with the largest effect on apo AIV levels was that detected with XbaI in the apo AIV gene, but this association was not statistically significant. Previously reported associations between the SstI polymorphism and triglyceride levels, and between the PstI polymorphism and apo AI levels, were weakly detected in the present sample. Our results show that variation associated with some of the polymorphisms in the apo AI-CIII-AIV cluster makes a small, but statistically significant, contribution to the determination of apo AI and apo CIII levels in this sample of young men and boys. These observations may, in part, explain reported associations between polymorphisms in this gene cluster, differences in plasma lipid and lipoprotein levels, and prevalence of coronary artery disease.
Paul-Hayase
H
H
Charing Cross Sunley Research Centre, Hammersmith, London, UK.
Rosseneu
M
M
Robinson
D
D
Van Bervliet
J P
JP
Deslypere
J P
JP
Humphries
S E
SE
D000293:Adolescent; D000328:Adult; D016632:Apolipoprotein A-I / Q000235:genetics*; D053304:Apolipoprotein C-II; D001053:Apolipoproteins / Q000097:blood; D001054:Apolipoproteins A / Q000235:genetics*; D001056:Apolipoproteins C / Q000097:blood / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D014644:Genetic Variation; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000502:physiology; D008055:Lipids / Q000097:blood; D008969:Molecular Sequence Data; D005810:Multigene Family; D009838:Oligodeoxyribonucleotides; D011110:Polymorphism, Genetic; D015183:Restriction Mapping
D016632:Apolipoprotein A-I; D053304:Apolipoprotein C-II; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D008055:Lipids; D009838:Oligodeoxyribonucleotides; C022205:apolipoprotein A-IV; D004247:DNA