Genética e epidemiologia da degeneração macular relacionada à idade: avaliação da variante rs1143627(–31G> A) do gene IL1β e análise do perfil epidemiológico em amostras da população brasileira de hospitais terciários

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over the age of 50 in developed countries. The disease is represented by a maculopathy of multifactorial cause that involves genetic, environmental, and constitutional factors not yet fully understood, associated with a chronic low-grade inflammatory profile characterized by the presence of immune cells and cytokines in the retina and vitreous humor. Currently, the association of genetic variants with increased risk and progression of the disease paves the way for the understanding of the pathophysiology of AMD and for the possibility of individualized therapies. The present study had two objectives. The first was to evaluate the association between AMD and the presence of the genetic variant rs1143627 (G>A) in the interleukin 1β gene, through a case-control study, from the blood collection of 397 patients with AMD and 402 individuals without AMD disease, residing in the states of São Paulo, Rio de Janeiro and Ceará. Genotyping was performed using the real-time polymerase chain reaction (RT-PCR) method and direct sequencing to confirm the data found. The frequency of the variant allele (A) was approximately 61% in the studied sample, similar to that described in European populations. No significant difference was observed when comparing the three genotypes (p = 0.21), but in the presence of one or two copies of the variant A allele (GA + AA) there was a tendency towards an increased risk for disease progression (OR = 1.47, 95% CI 0.96 – 2.27, p = 0.07), as well as a higher frequency of the variant allele in the group with neovascular AMD (OR = 1.23, 95% CI 0 .96 – 1.56, p = 0.08). Furthermore, the female group had a significantly higher frequency of the variant allele (OR = 1.46, 95% CI 1.12 – 1.91, p = 0.004). The second objective of the study was to analyze the epidemiological profile and the assessment of disease progression in 60 patients with AMD at a university hospital in the city of Rio de Janeiro, based on interviews and ophthalmological examinations. It was observed that increasing age and smoking, risk factors well established in the literature for the disease, were also the most significant for the evolution of AMD in the studied group.