title: rs5888 variant of SCARB1 gene is a possible susceptibility factor for age-related macular degeneration.
abstract: Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, including variants in the CFH gene and the ARMS2 LOC387715/HTRA1locus. Our purpose was to perform a case-control study in two populations among individuals who did not carry risk variants for CFHY402H and LOC387715 A69S (ARMS2), called "study" individuals, in order to identify new genetic risk factors. Based on a candidate gene approach, we analyzed SNP rs5888 of the SCARB1 gene, coding for SRBI, which is involved in the lipid and lutein pathways. This study was conducted in a French series of 1241 AMD patients and 297 controls, and in a North American series of 1257 patients with advanced AMD and 1732 controls. Among these individuals, we identified 61 French patients, 77 French controls, 85 North American patients and 338 North American controls who did not carry the CFH nor ARMS2 polymorphisms. An association between AMD and the SCARB1 gene was seen among the study subjects. The genotypic distribution of the rs5888 polymorphism was significantly different between cases and controls in the French population (p<0.006). Heterozygosity at the rs5888 SNP increased risk of AMD compared to the CC genotypes in the French study population (odds ratio (OR) = 3.5, CI95%: 1.4-8.9, p<0.01) and after pooling the 2 populations (OR = 2.9, 95% CI: 1.6-5.3, p<0.002). Subgroup analysis in exudative forms of AMD revealed a pooled OR of 3.6 for individuals heterozygous for rs5888 (95% CI: 1.7-7.6, p<0.0015). These results suggest the possible contribution of SCARB1, a new genetic factor in AMD, and implicate a role for cholesterol and antioxidant micronutrient (lutein and vitamin E) metabolism in AMD.
authors.affiliation: Creteil University Eye Clinic, Faculte de Medecine Henri Mondor, Creteil, France.
authors.forename: Jennyfer
authors.initials: J
authors.lastname: Zerbib
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Seddon
authors.forename: Florence
authors.initials: F
authors.lastname: Richard
authors.forename: Robyn
authors.initials: R
authors.lastname: Reynolds
authors.forename: Nicolas
authors.initials: N
authors.lastname: Leveziel
authors.forename: Pascale
authors.initials: P
authors.lastname: Benlian
authors.forename: Patrick
authors.initials: P
authors.lastname: Borel
authors.forename: Josué
authors.initials: J
authors.lastname: Feingold
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Gisèle
authors.initials: G
authors.lastname: Soubrane
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rozet
authors.forename: Eric H
authors.initials: EH
authors.lastname: Souied
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D014975:Lutein / Q000737:chemistry; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000502:physiology*
chemical_list: D008055:Lipids; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014975:Lutein