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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--&gt;A, G-630--&gt; A, T-625--&gt;deletion, C-482--&gt;T, and T-455--&gt;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 &lt; 0.0025). These results support the existence of apolipoprotein CIII promoter/Sst I haplotypes conferring either protection against or susceptibility to severe HTG.

An apolipoprotein CIII haplotype protective against hypertriglyceridemia is specified by promoter and 3' untranslated region polymorphisms.