Novel mutations in scavenger receptor BI associated with high HDL cholesterol in humans.

TitleNovel mutations in scavenger receptor BI associated with high HDL cholesterol in humans.
Publication TypeJournal Article
Year of Publication2011
AuthorsBrunham, LR, Tietjen, I, Bochem, AE, Singaraja, RR, Franchini, PL, Radomski, C, Mattice, M, Legendre, A, Hovingh, GK, Kastelein, JJP, Hayden, MR
JournalClin Genet
Volume79
Issue6
Pagination575-81
Date Published2011 Jun
ISSN1399-0004
KeywordsAdolescent, Adult, Aged, Animals, Base Sequence, Case-Control Studies, Cholesterol, HDL, Conserved Sequence, DNA Mutational Analysis, Female, Genetic Association Studies, Heterozygote, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Missense, Pedigree, Protein Structure, Tertiary, Scavenger Receptors, Class B, Sequence Alignment, Young Adult
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.

DOI10.1111/j.1399-0004.2011.01682.x
Alternate JournalClin. Genet.
PubMed ID21480869