Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary artery disease.
Data from various laboratories have indicated associations of various alleles determined by RFLPs within or adjacent to several apolipoprotein genes with abnormalities in plasma lipids and/or premature coronary artery disease (CAD). In order to assess such relationships we have examined allele frequencies of 8 different RFLPs within or adjacent to the apo A-I, C-III and A-IV gene complex on the long arm of chromosome 11 (MspI, 5' to the apo A-I gene; MspI, within the apo A-I gene; PstI, 3' to the apo A-I gene; SstI, 3' to the apo C-III gene; PvuII, within the apo C-III gene; PvuII, 5' to the apo C-III gene; XbaI, within the apo A-IV gene; and XbaI, 3' to the apo A-IV gene) in 202 patients with CAD (50% narrowing of one or more coronary arteries) prior to age 60 and 145 normal controls. None of the allele frequencies of these RFLPs were significantly different in cases as compared to controls. With regard to associations with plasma lipids and apolipoprotein levels, the rare allele determined by the absence of the PstI site was associated with elevated triglyceride levels (P less than 0.05) in cases, but not in controls. In contrast, the rate MspI allele 5' to the apo A-I gene was associated with elevated triglyceride levels (P less than 0.05) in controls but not in cases. In both cases and controls, subjects with the uncommon SstI allele had triglyceride levels that were 9 and 38% higher than in those without this allele. These differences were significant (P less than 0.05) only in controls. Our data indicate that the rare allele determined by the SstI site within this gene complex deserves further study in order to understand its association with elevated triglycerides in Caucasian populations. However, at the present time all these DNA markers lack sufficient specificity to be clinically useful for CAD risk assessment.
Lipid Metabolism Laboratory, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.
J M
JM
Ordovas
F
F
Civeira
J
J
Genest
S
S
Craig
A H
AH
Robbins
T
T
Meade
M
M
Pocovi
P M
PM
Frossard
U
U
Masharani
P W
PW
Wilson
D000367:Age Factors; D000483:Alleles; D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics; D001056:Apolipoproteins C / Q000235:genetics; D002874:Chromosome Mapping; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D008055:Lipids; C022205:apolipoprotein A-IV