Population-based study of SR-BI genetic variation and lipid profile.
The variability of the Class B Type I Scavenger Receptor (SR-BI) gene in human populations and the relation of its variants to blood lipids was investigated in a random sample of 1756 untreated adult residents of Geneva, Switzerland, during 1999-2000. A three-step study approach yielded the following results: (1) resequencing the gene's exons and flanking regions in 95 subjects identified four common single nucleotide polymorphisms (SNPs with rare allele frequency >3%); (2) association study of the four common SNPs in subjects with extreme HDL-cholesterol (HDL-C) and LDL-C phenotypes (186 "atherogenic cases" and 185 "non-atherogenic controls") showed that the synonymous exon 8 C-T (allelic frequency 48%) polymorphism, A350A, was associated with atheroprotection in men (odds ratios (OR) = 0.36, 95% confidence intervals (CI) = 0.15-0.90, P < 0.03), but not in women (2.09, 0.79-5.49, P = 0.14); and (3) population clinical effects of A350A genotypes assessed in all 1756 subjects, showed that the case-control study findings reflected a protective HDL-C effect in men (CC: 1.17 mmol/L, CT: 1.22 mmol/L, and TT: 1.24 mmol/L, trend P = 0.0062) and a deleterious LDL-C effect in women (CC: 3.58 mmol/L, CT: 3.72 mmol/L, and TT: 3.79 mmol/L, trend P = 0.014). The allelic frequencies of the common SR-BI variants appear to be very similar in European and North American populations. The HDL-C effect increased with age. SR-BI A350A appears to have gender-specific and age-related effects on cholesterol transport lipoproteins.
Morabia
Alfredo
A
Division of Clinical Epidemiology, Geneva University Hospitals, 25 rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. alfredo.morabia@hcuge.ch
Ross
Barbara M
BM
Costanza
Michael C
MC
Cayanis
Eftihia
E
Flaherty
Maria Sol
MS
Alvin
Gabriela B
GB
Das
Kamna
K
James
Richard
R
Yang
An-Suei
AS
Evagrafov
Oleg
O
Gilliam
T Conrad
TC
D000328:Adult; D000368:Aged; D018955:CD36 Antigens / Q000235:genetics; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B