An apolipoprotein CIII haplotype protective against hypertriglyceridemia is specified by promoter and 3' untranslated region polymorphisms.
Five DNA polymorphisms were detected in the promoter of the apolipoprotein CIII gene of a type III hyperlipidemic subject with severe hypertriglyceridemia (HTG). The polymorphic sites were C-641-->A, G-630--> A, T-625-->deletion, C-482-->T, and T-455-->C, with the previously reported base at each site designated allele 1 and the variant base designated allele 2. The sites were in strong linkage disequilibrium with each other and with a polymorphic Sst I site in the apolipoprotein CIII 3' untranslated region whose presence (S2 allele) has previously been shown to be associated with HTG. The distribution of haplotypes of the form -625 -482 Sst I among 78 normolipidemic adults and 79 adults with severe HTG was estimated by maximum likelihood analysis. The 211 haplotype was estimated to be 3.8-fold more common in normal subjects than in HTG subjects (estimated proportions, 0.186 and 0.049, respectively). This haplotype was associated with reduced HTG risk (relative risk, 0.28; P = 0.005) when compared with other haplotypes lacking the Sst I site (S1 allele). The 222 haplotype was estimated to be present on 48 of the 54 S2-containing chromosomes observed and was associated with increased risk for HTG (relative risk, 3.14; P < 0.0025). These results support the existence of apolipoprotein CIII promoter/Sst I haplotypes conferring either protection against or susceptibility to severe HTG.
Dammerman
M
M
Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY 10021-6399.
Sandkuijl
L A
LA
Halaas
J L
JL
Chung
W
W
Breslow
J L
JL
D000483:Alleles; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D001483:Base Sequence; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D015345:Oligonucleotide Probes; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes