Association of SALL1 rs1362756 and SIX1/SIX6 rs33912345 variants with POAG in a Brazilian population

Abstract

Purpose : PURPOSE: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide. Single nucleotide variants (SNV) identified through genome-wide association studies (GWAS) have been related with POAG risk and endophenotypes in different populations. SALL1 gene rs1362756 was associated with optic disc area and with the risk of POAG in patients of European ancestry. SIX1/SIX 6 rs33912345 has been associated with POAG risk in patients of European and Asian ancestry. No studies have been performed in heterogeneous populations such as Brazilian. Therefore, the aim of the present study was to investigate the association of SALL1 rs1362756 and SIX1/SIX6 rs33912345 with the risk of POAG development in a sample of the Brazilian population.

Methods : METHODS: A case-control study was performed with 600 subjects, encompassing 300 POAG patients and 300 controls. Complete ophthalmic evaluation was performed for both groups. SNVs genotyping was performed through Taqman® assays and the results were confirmed by Sanger sequencing in 10% of the samples from each group. The association of the SNVs was tested by chi-square test and logistic regression.

Results : RESULTS: We identified the association of rs33912345 variant of the SIX1/SIX6 gene with POAG development in the presence of the C allele (p=0.0482; OR=1.501; 95% CI=1.003-2.245). In the presence of the CC genotype the risk of developing POAG was even higher (p=0.0170; OR=1.877; 95% CI=1.190-2.961). No significant association was observed for rs1362756 of the SALL1 gene (p=0.0787; OR=1.343; 95% CI=0.969-1.862). However, in the presence of the CC genotype of SIX1/SIX6 rs33912345 and the CC genotype of SALL1 rs1362756 an additive effect was observed (p=5.629; OR=1.877-16.881).

Conclusions : CONCLUSION: Our study confirms the association of the SNV rs33912345 of the SIX1/SIX6 gene with POAG risk in a sample of the Brazilian population and an additive effect when rs33912345 and rs1362756 are analyzed simultaneously. This is an important finding for future diagnosis and treatment strategies for the Brazilian population. Further studies are needed to evaluate the frequency of these variants based on ancestry analyses.

This is a 2020 ARVO Annual Meeting abstract.