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.
Juo
S H
SH
National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA.
Bredie
S J
SJ
Kiemeney
L A
LA
Demacker
P N
PN
Stalenhoef
A F
AF
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