Association of genetic variants rs641153 (CFB), rs2230199 (C3), and rs1410996 (CFH) with age-related macular degeneration in a Brazilian population

Jamil M Neto; Marina Gm Viturino; Galina Ananina; Flávia F Bajano; Sueli M da S Costa; Alicia B Roque; Gessica Fs Borges; Raissa Franchi; Priscila Hh Rim; Flávio M Medina; Fernando F Costa; Mônica B de Melo; José Pc de Vasconcellos

doi:10.1177/15353702211024543

Association of genetic variants rs641153 (CFB), rs2230199 (C3), and rs1410996 (CFH) with age-related macular degeneration in a Brazilian population

Exp Biol Med (Maywood). 2021 Nov;246(21):2290-2296. doi: 10.1177/15353702211024543. Epub 2021 Jul 7.

Affiliations

¹ Department of Ophthalmology, Faculty of Medical Sciences - University of Campinas - Campinas, SP 13083-887, Brazil.
² Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG) - University of Campinas - Campinas, SP 13083-875, Brazil.
³ Department of Ophthalmology, Faculty of Medical Sciences, University of State of Rio de Janeiro - Rio de Janeiro, RJ 20551-030, Brazil.
⁴ Hematology and Hemotherapy Center - University of Campinas - Campinas, SP 13083-878, Brazil.

Abstract

This study aimed to investigate the association among genetic variants of the complement pathway CFB R32Q (rs641153), C3 R102G (rs2230199), and CFH (rs1410996) with age-related macular degeneration (AMD) in a sample of the Brazilian population. In a case-control study, 484 AMD patients were classified according to the clinical age-related maculopathy grading system (CARMS) and compared to 479 unrelated controls. The genetic variants rs1410996 of complement H (CFH), rs641153 of complement factor B (CFB), and rs2230199 of complement 3 (C3) were evaluated through polymerase chain reaction (PCR) and direct sequencing. The associations between single nucleotide polymorphisms (SNPs) and AMD, adjusted by age, were assessed by using logistic regression models. A statistically significant association was observed between AMD risk and rs2230199 variant with an OR of 2.01 (P = 0.0002) for CG individuals compared to CC individuals. Regarding the comparison of advanced AMD versus the control group, the OR was 2.12 (P = 0.0036) for GG versus AA genotypes for rs1410996 variant. Similarly, the OR for rs2230199 polymorphism was 2.3034 (P = 5.47^e-05) when comparing CG individuals to CC carriers. In contrast, the rs641153 variant showed a significant protective effect against advanced AMD for GA versus GG genotype (OR = 0.4406; P = 0.0019). When comparing wet AMD versus controls, a significant association was detected for rs1410996 variant (OR = 2.16; P = 0.0039) comparing carriers of the homozygous GG versus AA genotype, as well as in the comparisons of GG (OR = 3.0713; P = 0.0046) and CG genotypes (OR = 2.2249; P = 0.0002) versus CC genotype for rs2230199 variant, respectively. The rs641153 variant granted a significant protective effect against wet AMD for GA versus GG genotypes (OR = 0.4601; P = 0.0044). Our study confirmed the risk association between rs2230199 and rs1410996 variants and AMD, and the protective role against AMD for rs641153 variant.

Keywords: Complement pathway; age-related macular degeneration; genetic risk; rs1410996; rs2230199; rs641153.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Brazil
Case-Control Studies
Complement C3 / genetics*
Complement Factor B / genetics*
Complement Factor H / genetics*
Female
Gene Frequency / genetics
Genetic Predisposition to Disease / genetics
Genotyping Techniques
Humans
Macular Degeneration / genetics*
Male
Middle Aged
Polymerase Chain Reaction
Polymorphism, Single Nucleotide* / genetics

Substances

Complement C3
Complement Factor H
Complement Factor B