A major gene for primary hypoalphalipoproteinemia.
Sixteen kindreds were ascertained through probands clinically determined to have primary hypoalphalipoproteinemia, characterized by bottom decile high-density lipoprotein cholesterol (HDL-c), but otherwise normolipidemic. Age- and sex-adjusted, standardized HDL-c levels on 64 individuals in 14 nuclear families in which the proband was a parent were analyzed using the unified mixed model of segregation analysis as implemented in the computer program POINTER. The analysis proceeded by using the likelihood of offspring conditional on the parental phenotypes (conditional likelihood), which appears to overcome the limitation of possible heterogeneity in the selection criteria and provides an appropriate correction for the ascertainment. In these families, the multifactorial contribution to the phenotype appears to be small and significant only in the offspring generation. Although it was not possible to resolve the dominance pattern at the major locus since none of a recessive, additive, or dominant hypothesis could be firmly rejected, these families provided clear evidence for a major gene. Genetic heterogeneity is still a possibility, even within "primary" hypoalphalipoproteinemia.
D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D014644:Genetic Variation; D006801:Humans; D007009:Hypolipoproteinemias / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D011336:Probability; D012306:Risk; D013631:Tangier Disease / Q000097:blood / Q000235:genetics*
D008076:Cholesterol, HDL