title: Heritability and genetic loci of fatty liver in familial combined hyperlipidemia.
abstract: VLDL overproduction, a process that is driven by an excess amount of hepatic fat, is a well-documented feature of familial combined hyperlipidemia (FCHL). The aims of this study were to investigate whether fatty liver, measured with ultrasound and as plasma alanine aminotransferase (ALT) levels, develops against a genetic background in FCHL and to identify chromosomal loci that are linked to these traits. In total, 157 FCHL family members and 20 spouses participated in this study. Radiological evidence of fatty liver was more prevalent not only in FCHL probands (40%) but also in their relatives (35%) compared with spouses (15%) (P < 0.05). Heritability calculations revealed that 20-36% of the variability in ALT levels could be attributed to genetic factors. Nonparametric quantitative trait locus (QTL) analysis revealed three significant (P < 0.001) loci with either the ultrasound or the ALT trait in the male sample: 1q42.3, 7p12-21, and 22p13-q11; none was found in the female sample or the entire group. Of these QTLs, the 7p region was consistent over time, because reanalysis with ALT levels that were determined during a visit 5 years earlier yielded similar results. This study shows that fatty liver is a heritable aspect of FCHL. Replication of particularly the 7p region is awaited.
authors.affiliation: Department of Medicine and Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, Maastricht, The Netherlands. martijn.brouwers@intmed.unimaas.nl
authors.forename: Martijn C G J
authors.initials: MC
authors.lastname: Brouwers
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Naoko
authors.initials: N
authors.lastname: Kono
authors.forename: Jeong Lim
authors.initials: JL
authors.lastname: Yoon
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: Monique A L
authors.initials: MA
authors.lastname: Bilderbeek-Beckers
authors.forename: Marleen M J
authors.initials: MM
authors.lastname: van Greevenbroek
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Tjerk W A
authors.initials: TW
authors.lastname: de Bruin
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005234:Fatty Liver / Q000097:blood / Q000209:etiology* / Q000235:genetics*; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000097:blood / Q000235:genetics
chemical_list: D014280:Triglycerides; D000410:Alanine Transaminase