title: G-->A substitution at position -75 of the apolipoprotein A-I gene promoter. Evidence against a direct effect on HDL cholesterol levels.
abstract: The present study sought to resolve the contradictory evidence as to whether the G-->A substitution at position -75 of the apoA-I gene promoter raises HDL cholesterol (HDL-C) levels by examining the effect of this polymorphism in French Canadians, a relatively genetically homogeneous population. Among 308 women, carriers of the A allele displayed 12% and 10% higher mean plasma HDL-C and apoA-I concentrations, respectively, than did noncarriers. Among 345 men, no effect of the A allele was noted. The frequency distribution of HDL-C levels in women carrying the A but not the G allele appeared bimodal, with one peak corresponding to the mean of the noncarriers and a second to higher HDL-C. Thus it appears that only a subset of A alleles confers high HDL-C levels. This hypothesis was supported by data from four kindreds within which some but not all A alleles segregated with hyperalphalipoproteinemia. The data suggest that the A substitution in the apoA-I gene promoter does not directly confer high HDL-C levels but may be in linkage disequilibrium with other sequence polymorphism(s) at this locus in a subset of alleles that raise HDL-C levels.
authors.affiliation: Clinical Research Institute of Montreal, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Minnich
authors.forename: G
authors.initials: G
authors.lastname: DeLangavant
authors.forename: J
authors.initials: J
authors.lastname: Lavigne
authors.forename: G
authors.initials: G
authors.lastname: Roederer
authors.forename: S
authors.initials: S
authors.lastname: Lussier-Cacan
authors.forename: J
authors.initials: J
authors.lastname: Davignon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016632:Apolipoprotein A-I / Q000235:genetics*; D001483:Base Sequence; D002170:Canada; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006951:Hyperlipoproteinemias / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL