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10 January 2018 : Clinical Research  

The Association Between Variants of Receptor for Advanced Glycation End Products (RAGE) Gene Polymorphisms and Age-Related Macular Degeneration

Mantas Banevicius1ABC, Alvita Vilkeviciute2CDEF, Loresa Kriauciuniene12ADG, Rasa Liutkeviciene12ABEG*, Vytenis Pranas Deltuva2ADG

DOI: 10.12659/MSM.905311

Med Sci Monit 2018; 24: CLR190-199

Abstract

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in people aged 65 years and older in developed countries. The pathogenesis of AMD has been linked to mechanisms involving inflammation, oxidative stress, and basal laminar deposit formation between retinal pigment epithelium (RPE) cells and the basal membrane, caused by advanced glycation end products (AGEs). AGEs are implicated in the pathogenesis of AMD through the AGE-and receptor for AGE (RAGE) interaction, which can be altered by polymorphisms of the RAGE gene. We examined RAGE rs1800624 and rs1800625 gene polymorphisms contributing to AMD development.

MATERIAL AND METHODS: The study enrolled 300 patients with early AMD, 300 patients with exudative AMD, and 800 healthy controls. The genotyping was carried out using the RT-PCR method.

RESULTS: The analysis of two single nucleotide polymorphisms (SNPs) in the RAGE gene showed that rs1800624 was associated with a 1.6-fold decreased risk for exudative AMD under the dominant model after adjustment for age (OR=0.616; 95% CI: 0.394–0.963; p=0.034) and each copy of allele T at rs1800624 was associated with a 1.4-fold decreased risk for exudative AMD development under the additive model after adjustment for age (OR=0.701; 95% CI: 0.510–0.962; p=0.028). Analysis revealed that the rs1800625 allele G at rs1800625 was associated with a 1.5-fold increased risk for exudative AMD after adjustment for age (OR=1.545; 95% CI: 1.003–2.379; p=0.048). These results suggested that the allele G at rs1800625 was a risk-allele for exudative AMD development. In haplotype analysis, A-G haplotype was significantly more frequently observed in exudative AMD patients compared to healthy controls (3.3% versus 1.4%, p=0.035).

CONCLUSIONS: We revealed a significant association between RAGE gene rs1800624 and rs1800625 polymorphisms and AMD risk. We considered T allele at rs1800624 to be protective against AMD development, while allele G at rs1800625 was considered to be a marker of poor prognosis in AMD development.

Keywords: Glycosylation End Products, Advanced, Macular Degeneration, Polymorphism, Genetic

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750