title: Novel mutations in scavenger receptor BI associated with high HDL cholesterol in humans.
abstract: The scavenger receptor class B, member 1 (SR-BI), is a key cellular receptor for high-density lipoprotein (HDL) in mice, but its relevance to human physiology has not been well established. Recently a family was reported with a mutation in the gene encoding SR-BI and high HDL cholesterol (HDL-C). Here we report two additional individuals with extremely high HDL-C (greater than the 90th percentile for age and gender) with rare mutations in the gene encoding SR-BI. These mutations segregate with high HDL-C in family members of each proband and are associated with a 37% increase in plasma HDL-C in heterozygous individuals carrying them. Both mutations occur at highly conserved positions in the large extracellular loop region of SR-BI and are predicted to impair the function of the SR-BI protein. Our findings, combined with the prior report of a single mutation in the gene encoding SR-BI, further validate that mutations in SR-BI are a rare but recurring cause of elevated HDL-C in humans.
authors.affiliation: Department of Medicine and Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada. liam@cmmt.ubc.ca
authors.forename: L R
authors.initials: LR
authors.lastname: Brunham
authors.forename: I
authors.initials: I
authors.lastname: Tietjen
authors.forename: A E
authors.initials: AE
authors.lastname: Bochem
authors.forename: R R
authors.initials: RR
authors.lastname: Singaraja
authors.forename: P L
authors.initials: PL
authors.lastname: Franchini
authors.forename: C
authors.initials: C
authors.lastname: Radomski
authors.forename: M
authors.initials: M
authors.lastname: Mattice
authors.forename: A
authors.initials: A
authors.lastname: Legendre
authors.forename: G K
authors.initials: GK
authors.lastname: Hovingh
authors.forename: J J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood*; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D017434:Protein Structure, Tertiary; D051122:Scavenger Receptors, Class B / Q000235:genetics*; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B