Analysis of CFB (R32Q - rs641153) and CFH (rs1410996) variants as risk factors for Age-related Macular Degeneration in a Brazilian population

Abstract

Purpose : Age-related macular degeneration (AMD) is a progressive, mutifactorial condition that affects the central retina, and represents an important cause of blindness in the elderly population worldwide. Its pathogenesis is complex, with genetics and environmental factors playing critical roles. The genetic component of AMD has been estimated at 45% to 70%, with at least 34 genomic loci implicated in its etiology. Different variants of complement pathway-associated genes have been associated with the disease, demonstrating the importance of immune pathology and inflammation in the mechanism of AMD. The purpose of this study was to evaluate the role of the variants CFB R32Q (rs641153) and CFH (rs1410996) in the risk of development of AMD in a Brazilian population.

Methods : This was a case-control study, in which 443 unrelated AMD patients and 471 controls were evaluated for the rs641153 and 451 unrelated AMD patients and 435 controls were evaluated for the rs1410996 SNPs through PCR/direct sequencing. AMD patients were diagnosed according to the International Classification System and subdivided in subgroups: dry and wet; early and advanced disease.

Results : Genotype distributions were significantly different when cases and controls were compared. When analyzing rs641153, AG/AA genotypes were more frequent in controls than in cases when compared to GG genotype (p= 0.0008), OR: 0.548 (IC95% 0.385-0.780). When comparing early versus advanced forms, GG genotype was more frequent in patients with advanced AMD (p=0.0006), OR: 1.878 (IC95% 1.081-3.262). No association was observed for the comparison of wet versus dry forms. For rs1410996, GG/AG genotypes were more frequent in cases than controls when compared to AA genotype (p=0.0296), OR: 1.462 (IC95% 1.038-2.059). For the comparison of GG versus AA genotype, OR was 2.030 (IC95% 1.375-2.996) (p=0.0002). No association was observed for the comparisons early versus advanced and dry versus wet AMD.

Conclusions : These results are in accordance with the literature and support the role of the A variant of the CFB gene in AMD susceptibility, as a protection factor for the disease and the G variant of the CFH gene as a risk factor for the disease. To our knowledge, this is the first report of the association of these variants with AMD in Brazilians, a highly admixed population.

This is a 2020 ARVO Annual Meeting abstract.