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.
Highlights
Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly population in Europe and United States [1,2]
The genotypic distributions of the CFH Y402H and ARMS2 single nucleotide polymorphisms (SNPs) were significantly different between cases and controls in both the French and North American series (p,0.0001 for both groups)
The distribution of the SCARB1 rs5888 genotype was significantly different in the North American AMD population compared to controls (p,0.004): CT heterozygotes were at increased risk of AMD compared to CC subjects, TT did not significantly differ from CC.Similar results were obtained after pooling the French and the North American population: adjusted ORCT vs CC = 1.3, 95% confidence interval (95%CI): 1.0–1.7) and adjusted ORTT vs CC = 1.2, 95%CI 0.9–1.7
Summary
Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly population in Europe and United States [1,2]. Over the past few years, several single nucleotide polymorphisms (SNPs) have been associated with AMD, including variants in the CFH and ARMS2 genes [15,16,17,18,19,20,21,22,23,24,25,26,64]. The association between these polymorphisms and AMD risk suggests a pathway of inflammation and oxidation in AMD. Several lines of evidence suggest a strong role of antioxidant micronutrients (xanthophylls, vitamin E and vitamin C) and lipids in AMD [8,27,28,29,30,31,32,33]
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