title: Inheritance pattern of familial hypercholesterolemia and markers of cardiovascular risk.
abstract: Studies in children and adults have resulted in conflicting evidence in the quest for the answer to the hypothesis that offspring from hypercholesterolemic mothers might have an increased cardiovascular risk. Previous studies might have suffered from limitations such as cohort size and clinical sampling bias. We therefore explored this hypothesis in large cohorts of both subjects with familial hypercholesterolemia (FH) and unaffected siblings in a wide age range. In three cohorts (cohort 1: n = 1,988, aged 0-18 years; cohort 2: n = 300, 8-30 years; cohort 3: n = 369, 18-60 years), we measured lipid and lipoproteins as well as carotid intima-media thickness (c-IMT) in offspring from FH mothers versus FH fathers. For LDL cholesterol, triglycerides (TGs), and c-IMT, we performed a pooled analysis. No significant differences could be observed in c-IMT, lipid, or lipoprotein levels from offspring of FH mothers versus FH fathers. Pooled analyses showed no significant differences for either LDL cholesterol [mean difference 0.02 (-0.06,0.11) mmol/l, P = 0.60], TGs [mean difference 0.07 (0.00,0.14) mmol/l, P = 0.08], or c-IMT [mean difference -0.00 (-0.01,0.01) mm, P = 0.86]. Our data do not support the hypothesis that cardiovascular risk markers are different between offspring from FH mothers and FH fathers.
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: D Meeike
authors.initials: DM
authors.lastname: Kusters
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Avis
authors.forename: Marjet J
authors.initials: MJ
authors.lastname: Braamskamp
authors.forename: Roeland
authors.initials: R
authors.lastname: Huijgen
authors.forename: Frits A
authors.initials: FA
authors.lastname: Wijburg
authors.forename: John J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Albert
authors.initials: A
authors.lastname: Wiegman
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000150:complications*; D059168:Carotid Intima-Media Thickness; D002648:Child; D002675:Child, Preschool; D005220:Fathers; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007223:Infant; D007231:Infant, Newborn; D040582:Inheritance Patterns; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D009035:Mothers; D012306:Risk; D035781:Siblings
chemical_list: D015415:Biomarkers; D008074:Lipoproteins
keywords: atherosclerosis; dyslipidemias; epigenetics; lipids; lipoproteins; pregnancy