Abstract
Purpose :
Age-related macular degeneration (AMD), a multifactorial disease, results from an amalgamation of genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in specific genes have been implicated in AMD in varying populations. However, their role in the Indian population remains elusive. We tested the hypothesis that SNPs in these genes would be associated with AMD.
Methods :
The study followed a case-control design. 150 AMD patients and 84 controls were recruited from the Advanced eye centre, Post graduate institute of medical education and research after screening by an Ophthalmologist. ELISA was used to estimate the protein expression of these genes in the serum of AMD patients and controls. Taqman genotyping assay was used for genotyping SNPs of ARMS2, COL10A1, RAD51B and TGFBR1. SPSS ver. 21.0 was used for the analysis. The Chi-square test was used for the analysis of genotyping data. Mann-Whitney or T test was used for the analysis of protein data depending on the distribution of data. Binary logistic regression was used for calculating Odds ratios. p≤0.05 was considered statistically significant.
Results :
The frequency of ARMS2 rs10490924T allele was higher in AMD than in controls (p=0.001). Allele T was over-represented in AMD subjects compared to controls(p≤0.001). The risk nature of the T allele and TT genotype was further supported by dominant (p=0.009) and recessive (p=0.001) models. For rs1064583, in COL10A1, the AG genotype was under-represented in AMD compared to controls (p=0.004). The allelic distribution indicated a lower frequency of the G allele in AMD compared to the control group (p=0.007). The protective nature of rs1064583G allele was further confirmed by the dominant (p=0.002) and over-dominant models (p=0.033). For RAD51B rs8017304, we did not find any significant differences in genotypic and allelic frequencies. For TGFBR1, rs334353, the over-dominant model revealed that the GT genotype was under-represented in AMD (p=0.036) compared to controls. ELISA results showed that the expression of COL10A1 was significantly higher in AMD(p≤0.0001), whereas RAD51B(p≤0.0001) and TGFBR1(p=0.002) levels were significantly lower in AMD compared to controls.
Conclusions :
SNPs in ARMS2 and COL10A1 are associated with AMD in the Indian population. Also, the expression of COL10A1, RAD51B and TGFBR1 is altered in AMD compared to controls indicating their role in the pathophysiology of AMD.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.