A common genetic mechanism determines plasma apolipoprotein B levels and dense LDL subfraction distribution in familial combined hyperlipidemia.
Familial combined hyperlipidemia (FCH) is a common lipid disorder characterized by elevations of plasma cholesterol and/or triglyceride in first-degree relatives. A predominance of small, dense LDL particles and elevated apolipoprotein B (apoB) levels is commonly found in members of FCH families. Many studies have investigated the genetic mechanisms determining individuals' lipid levels, in FCH families. Previously, we demonstrated a major gene effect on LDL particle size and codominant Mendelian inheritance involved in determination of apoB levels in a sample of 40 well-defined FCH families. An elevation of apoB levels is associated metabolically with a predominance of small, dense LDL particles in FCH. To establish whether a common gene regulates both traits, we conducted a bivariate genetic analysis to test the hypothesis of a common genetic mechanism. In this study, we found that 66% of the total phenotypic correlation is due to shared genetic components. Further bivariate segregation analysis suggested that both traits share a common major gene plus individual polygenic components. This common major gene explains 37% of the variance of adjusted LDL particle size and 23% of the variance of adjusted apoB levels. Our study suggests that a major gene that has pleiotropic effects on LDL particle size and apoB levels may be the gene underlying FCH in the families we studied.
National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA.
S H
SH
Juo
S J
SJ
Bredie
L A
LA
Kiemeney
P N
PN
Demacker
A F
AF
Stalenhoef
D001055:Apolipoproteins B / Q000097:blood* / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D005190:Family; D005799:Genes, Dominant; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000235:genetics*; D016013:Likelihood Functions; D008077:Lipoproteins, LDL / Q000097:blood* / Q000235:genetics*; D008957:Models, Genetic; D015233:Models, Statistical; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol