title: Genetic influences contributing to LDL particle size in familial combined hyperlipidaemia.
abstract: The nature of the genetic and environmental factors influencing low density lipoprotein (LDL) particle size in patients with familial combined hyperlipidaemia (FCHL) is under debate. We measured LDL peak particle size in 553 subjects belonging to 48 Finnish FCHL families. Individuals with high triglyceride (TG) concentrations (phenotype IV) or combined hyperlipidaemia (phenotype IIB) had significantly smaller LDL particles than those with hypercholesterolaemia (phenotype IIA) or unaffected subjects (P<0.001). In stepwise regression analyses, serum TGs (r(2)=43%, P<0.001) and high density lipoprotein cholesterol (HDL-C) (r(2)=4.5%, P<0.001) were the only significant predictors of LDL peak particle size. Familial correlations support the conclusion that LDL peak particle size is familial, and most probably influenced by genes in these families. Segregation analysis of LDL peak particle size, a quantitative trait, was performed to model this genetic influence. Our results suggest a polygenic background for LDL size with a recessive major gene that may contribute to large LDL peak particle size in women. Serum TG and HDL-C concentrations predict the majority of variations in LDL particle size.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Vakkilainen
authors.forename: Päivi
authors.initials: P
authors.lastname: Pajukanta
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Ilpo O
authors.initials: IO
authors.lastname: Nuotio
authors.forename: Sanni
authors.initials: S
authors.lastname: Lahdenperä
authors.forename: Kati
authors.initials: K
authors.lastname: Ylitalo
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Jorma S A
authors.initials: JS
authors.lastname: Viikari
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D004777:Environment; D005190:Family; D005260:Female; D005387:Finland; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood / Q000235:genetics*; D008297:Male; D008970:Molecular Weight; D010641:Phenotype; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides