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Familial hypertriglyceridemia has been suggested to be an autosomal dominant condition with age-dependent penetrance, but so far the underlying defective gene has not been elucidated. We examined the possible role of three candidate gene loci by linkage analysis in six Finnish families with familial clustering of hypertriglyceridemia. The probands were initially recruited from a group of hyperlipidemic outpatients after measurement of serum triglyceride concentrations exceeding 2.00 mmol/l on two occasions. Altogether, 71 subjects were included in the linkage analyses. Bior multiallelic DNA polymorphisms were used as markers for the apolipoprotein B gene (chromosome 2), lipoprotein lipase gene (chromosome 8), and apolipoprotein A-I/C-III/A-IV gene cluster (chromosome 11). Linkage analysis was performed by applying two alternative phenotyping models, one adopting quantitative serum triglyceride concentrations and another using qualitative classification of the subjects into hypertriglyceridemic, normotriglyceridemic, and borderline hypertriglyceridemic groups. Using either approach, the cumulative lod scores of each of the three candidate genes in the six families were less than -2.0 at the recombination fraction 0.0. These results suggest that none of the candidate genes investigated is involved in familial clustering of hypertriglyceridemia in our study.

The genetic variation of apolipoprotein B has been studied extensively in Finns with the aid of protein and DNA polymorphisms. Population association studies confirmed significant associations between the Xbal polymorphism of the apolipoprotein B gene and elevated serum cholesterol levels, and dietary studies suggested that the Xbal and ins/del polymorphisms might modify the serum lipid response to dietary fat intake. Studies comparing patients and controls, however, did not confirm previous studies suggesting that the multiallelic variation at the 3'VNTR region of the apolipoprotein B gene was associated with coronary artery disease. The results suggest that the apolipoprotein B gene is involved in the regulation of serum lipid levels. A yet unknown mutation in linkage disequilibrium with the Xbal site may contribute to this regulation.