Associations of cholesteryl ester transfer protein (CETP) gene variants with predisposition to age-related macular degeneration

摘要

Abstract Purpose To determine the frequency of the genotypes of single nucleotide polymorphisms (SNPs) in the gene encoding cholesteryl ester transfer protein (CETP) and their associations with age-related macular degeneration (AMD) in the Lithuanian population. Study design A total of 1264 subjects were examined: 251 patients with early AMD, 206 patients with exudative AMD, and 807 healthy controls. Methods The genotyping of CETP (rs5882, rs708272, rs3764261, rs1800775, rs2303790) was carried out using the RT-PCR. Results Binomial logistic regression analysis revealed that each copy of rs5882 allele A was associated with a 1.3-fold increased risk of exudative AMD (p=0.046). The G/A and A/A genotypes of the rs708272 polymorphism were associated with 1.5-fold and 1.7-fold increased risks of exudative AMD (p=0.049 and p=0.021, respectively). Combination of two genotypes (G/A+A/A) under the dominant model were associated with a 1.5-fold increased risk of exudative AMD (p=0.021). Analysis of rs708272 revealed that the G/A and A/A genotypes under the co-dominant model were associated with 1.5-fold and 1.7-fold increased risks of exudative AMD, respectively (OR=1.450, 95% CI=1.002–2.098; p=0.049 and OR=1.710, 95% CI=1.064–2.156; p=0.021, respectively). Both genotypes (G/A+A/A) under the dominant model were associated with the 1.5-fold increased risk of exudative AMD, as well (OR=1.514, 95% CI=1.064–2.156; p=0.021) and each additional copy A allele was associated with a 1.3-fold increased risk of exudative AMD (OR=1.316, 95% CI=1.051–1.646; p=0.016). The rs3764261 polymorphism was identified to be protective: the C/A genotype and the combination of two genotypes (C/A+A/A) were associated with 1.8-fold and 1.5-fold decreased risks of exudative AMD (p=0.001 and p=0.015, respectively). Conclusion Our study identified two polymorphisms with a higher risk of AMD development (rs5882 and rs708272) and a protective polymorphism for AMD (rs3764261). Highlights ? To our knowledge it is the first time when CETP gene variants have been studied in the Baltic States. ? To our knowledge, this study was the first to analyze rs708272 in early and exudative AMD as well as rs5882 in early AMD. ? Only healthy patients without any systemic (non)infectious diseases were included into our study. ? rs5882 and rs708272 are associated with a higher risk of AMD development and rs3764261 is protective.