title: A cholesterol-lowering gene maps to chromosome 13q.
abstract: A cholesterol-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to those in persons with heterozygous FH. We studied such a family with FH that also had members without FH and with lower-than-normal LDL levels. We performed linkage analyses and identified a locus at 13q, defined by markers D13S156 and D13S158. FASTLINK and GENEHUNTER yielded LOD scores >5 and >4, respectively, whereas an affected-sib-pair analysis gave a peak multipoint LOD score of 4.8, corresponding to a P value of 1.26x10-6. A multipoint quantitative-trait-locus (QTL) linkage analysis with maximum-likelihood binomial QTL verified this locus as a QTL for LDL levels. To test the relevance of this QTL in an independent normal population, we studied MZ and DZ twin subjects. An MZ-DZ comparison confirmed genetic variance with regard to lipid concentrations. We then performed an identity-by-descent linkage analysis on the DZ twins, with markers at the 13q locus. We found strong evidence for linkage at this locus with LDL (P<.0002), HDL (P<.004), total cholesterol (P<.0002), and body-mass index (P<.0001). These data provide support for the existence of a new gene influencing lipid concentrations in humans.
authors.affiliation: Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine and Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Knoblauch
authors.forename: B
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: A
authors.initials: A
authors.lastname: Busjahn
authors.forename: L
authors.initials: L
authors.lastname: Ben Avi
authors.forename: S
authors.initials: S
authors.lastname: Bähring
authors.forename: H
authors.initials: H
authors.lastname: Baron
authors.forename: S C
authors.initials: SC
authors.lastname: Heath
authors.forename: R
authors.initials: R
authors.lastname: Uhlmann
authors.forename: H D
authors.initials: HD
authors.lastname: Faulhaber
authors.forename: S
authors.initials: S
authors.lastname: Shpitzen
authors.forename: A
authors.initials: A
authors.lastname: Aydin
authors.forename: A
authors.initials: A
authors.lastname: Reshef
authors.forename: M
authors.initials: M
authors.lastname: Rosenthal
authors.forename: O
authors.initials: O
authors.lastname: Eliav
authors.forename: A
authors.initials: A
authors.lastname: Mühl
authors.forename: A
authors.initials: A
authors.lastname: Lowe
authors.forename: D
authors.initials: D
authors.lastname: Schurr
authors.forename: D
authors.initials: D
authors.lastname: Harats
authors.forename: E
authors.initials: E
authors.lastname: Jeschke
authors.forename: Y
authors.initials: Y
authors.lastname: Friedlander
authors.forename: H
authors.initials: H
authors.lastname: Schuster
authors.forename: F C
authors.initials: FC
authors.lastname: Luft
authors.forename: E
authors.initials: E
authors.lastname: Leitersdorf
mesh_terms: D000328:Adult; D000367:Age Factors; D001055:Apolipoproteins B / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood / Q000235:genetics*; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D019655:Quantitative Trait, Heritable; D012737:Sex Factors
chemical_list: D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D002784:Cholesterol