The interactions between ARMS2, CFH, VEGF-A and environmental factors on the risk of age-related macular degeneration.

Background: Age related macular degeneration (AMD) is a multifactorial disease caused by a combination of environmental and genetic factors. The prevalence of allele and genotypeof AMD-related genes is varied throughout the world due to racial and ethnic differences. Number of previous studies have shown that the polymorphisms in the ARMS2, CFH and VEGF-A genes are associated with AMD. In Mongolia, there is a lack of sufficient data on AMD development in its population and thus needs more studies on the topic. Therefore, it needs more studies about AMD development in the population. For this reason, we have investigated several specified polymorphisms in CFH, VEGF-A and ARMS2 genes to reveal a relationship with AMD and determine the prevalence of alleles and genotypes of the genes in Mongolian population.

Methods: Totally 161 AMD patients and 223 controls were enrolled in this case-control study. The polymorphisms in CFH, ARMS2 and VEGF-A were detected by using the methods of allele-specific polymerase chain reaction (ASPCR) and PCR based restriction fragment length polymorphism (RFLP). Statistical analysis were performed by STATA 13.0, SNPAlyze 9.0 and MDR 3.0.2.

Results: According to the study result, the characteristics of hypertension, constant-wearing sunglasses and anticoagulant medications in AMD group were significantly different from those in the control group. As for the dominant model, T allele of ARMS2 rs10490924 (cOR=4.45; 95% CI, 2.44-8.13, p<0.001, aOR=5.08; 95% CI, 2.70-9.59, p<0.001) was more frequent among patients with AMD in comparison with the control group. Also, G/G genotype of CFH rs800292 (cOR=11.61; 95% CI, 3.41-39.51, p<0.001, aOR=12.49; 95% CI, 3.47-44.91, p<0.001) and G/G genotype of CFH rs1065489 (cOR=4.19; 95% CI, 2.53-6.93, p<0.001, aOR=4.67; 95% CI, 2.71-8.05, p<0.001) were significantly higher in AMD group after Bonferroni correction. This result suggests that people who carrying the risk genotypes of these polymorphisms had an increased risk for AMD development. As for the models of three or more SNP interactions, the participants with any combinations of risk genotypes have 6 to 106-fold higher risk for AMD development. This result suggests that there is some positive-additive interaction existing between the genetic variants of ARMS2, CFH and VEGF-A genes for AMD development. Our study also revealed that the participants with hypertension and carrying G/G for rs1065489 in CFH gene or non G/G for rs10490924 in ARMS2 gene genotypes had 9 to 14 times higher risk for AMD development (cOR=9.05; 95% CI, 4.38-18.68, p<0.001, RERI=4.546; AP=0.502, S=2.298, cOR=13.98; 95% CI, 3.19-61.1, p<0.001, RERI=5.85; AP=0.419, S=1.821) with high level of significance. Moreover, it was found that the participants who avoided wearing sunglasses and had the G/G genotype of ARMS2 rs10490924 or G/G genotype of CFH rs800292 had an extremely higher risk for AMD development (p<.001).

Conclusions: In conclusion, it was observed that the combination of SNPs in ARMS2, CFH and VEGF-A genes increase the risk for AMD with 6 to 106-fold. Moreover, we found that the participants with hypertension and carrying the non G/G genotype of ARMS2 rs10490924 or the G/G genotype of CFH rs800292 had an extremely higher risk of AMD development.