title: Maternal inheritance does not predict cholesterol levels in children with familial hypercholesterolemia.
abstract: OBJECTIVE
  Pregnancy exerts metabolic changes with increasing levels of total cholesterol and triglycerides as prominent features. Maternal hypercholesterolemia may thus contribute to an unfavorable in utero environment potentially influencing the susceptibility of adult cardiovascular disease in the offspring. We investigated the impact of maternal familial hypercholesterolemia (FH) on pre-treatment plasma lipids and C-reactive protein (CRP) levels in non-statin treated FH children.
  
  
  METHODS
  Children with FH (n = 1063) aged between 0 and 19 years were included. Of these, 500 had inherited FH maternally, 563 paternally and 97.6% had a verified FH mutation. Information about inheritance, mutation type and pretreatment levels of blood lipids and CRP was retrieved from the medical records.
  
  
  RESULTS
  There were no significant differences in the plasma levels of lipids and C-reactive protein (CRP) in children with maternal FH compared with children with paternal FH, (0.12 ≤ P ≤ 0.90). Independent of which parent transmitted FH, children with LDL receptor negative mutations had significantly higher levels of total and LDL cholesterol and Apolipoprotein (Apo) B, and lower levels of HDL cholesterol and ApoA1, compared with children with other LDL receptor mutations (P < 0.001).
  
  
  CONCLUSIONS
  Maternal inheritance of FH was not associated with detectable long-term effects in the offspring's phenotype measured by adverse lipid profiles and increased CRP levels, whereas a LDL receptor negative mutation was associated with an unfavorably phenotype in FH offspring. Our findings do not support the fetal origin of adulthood disease hypothesis, while at the same time not excluding the hypothesis since other pathways leading to atherosclerosis may be involved.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1046 Blindern, 0317, Oslo, Norway; Lipid Clinic, Oslo University Hospital Rikshospitalet, P.O Box 4950 Nydalen, 0424, Oslo, Norway.
authors.forename: Ingunn
authors.initials: I
authors.lastname: Narverud
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jeanine Roeters
authors.initials: JR
authors.lastname: van Lennep
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1046 Blindern, 0317, Oslo, Norway; Lipid Clinic, Oslo University Hospital Rikshospitalet, P.O Box 4950 Nydalen, 0424, Oslo, Norway.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Christensen
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jorie
authors.initials: J
authors.lastname: Versmissen
authors.affiliation: Oslo Centre for Biostatics and Epidemiology, Institute of Basic Medical Science, University of Oslo, Norway.
authors.forename: Jon Michael
authors.initials: JM
authors.lastname: Gran
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1046 Blindern, 0317, Oslo, Norway; Department of Haematology, Oslo University Hospital, P.O Box 4950 Nydalen, 0424, Oslo, Norway.
authors.forename: Per Ole
authors.initials: PO
authors.lastname: Iversen
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, P.O Box 4950 Nydalen, 0424, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, P.O Box 1171 Blindern, 0318, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, P.O Box 4950 Nydalen, 0424, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, P.O Box 1171 Blindern, 0318, Oslo, Norway; K.G. Jebsen TREC, The Faculty of Health Sciences, UiT- The Arctic University of Tromsø, 9037, Tromsø, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, P.O Box 4950 Nydalen, 0424, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, P.O Box 1171 Blindern, 0318, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, P.O Box 1171 Blindern, 0318, Oslo, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, P.O Box 4950 Nydalen, 0424, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, P.O Box 1171 Blindern, 0318, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, P.O Box 1171 Blindern, 0318, Oslo, Norway; K.G. Jebsen TREC, The Faculty of Health Sciences, UiT- The Arctic University of Tromsø, 9037, Tromsø, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Department of Health, Nutrition and Management, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, P.O Box 4, St. Olavs Plass, 0130, Oslo, Norway.
authors.forename: Stine M
authors.initials: SM
authors.lastname: Ulven
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1046 Blindern, 0317, Oslo, Norway; Lipid Clinic, Oslo University Hospital Rikshospitalet, P.O Box 4950 Nydalen, 0424, Oslo, Norway.
authors.forename: Leiv
authors.initials: L
authors.lastname: Ose
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1046 Blindern, 0317, Oslo, Norway; Oslo Centre for Biostatics and Epidemiology, Institute of Basic Medical Science, University of Oslo, Norway.
authors.forename: Marit B
authors.initials: MB
authors.lastname: Veierød
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Sijbrands
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1046 Blindern, 0317, Oslo, Norway; Lipid Clinic, Oslo University Hospital Rikshospitalet, P.O Box 4950 Nydalen, 0424, Oslo, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Retterstøl
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O Box 1046 Blindern, 0317, Oslo, Norway; Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Rikshospitalet, P.O Box 4950, Nydalen, Norway. Electronic address: kirsten.holven@medisin.uio.no.
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Holven
mesh_terms: D000293:Adolescent; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004252:DNA Mutational Analysis; D005220:Fathers; D005260:Female; D040941:Heredity; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation; D008055:Lipids / Q000097:blood; D008297:Male; D009035:Mothers; D009154:Mutation; D009664:Norway; D010641:Phenotype; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; D002097:C-Reactive Protein
keywords: Children; Familial hypercholesterolemia; LDL cholesterol; Maternal inheritance