"Association of APOE gene polymorphisms with primary open angle glaucoma in Brazilian patients".

Background: Primary open-angle glaucoma (POAG) is a multifactorial disease that affects 65.5 million people worldwide. In addition to the genetic variants already established as indicators of greater risk for POAG, the apolipoprotein (APOE) gene has been studied in some populations, with controversial results. The aim of this study is to investigate the frequency of the genetic variants of APOE in the Brazilian population, and to evaluate the association between these polymorphisms and the risk of POAG. Methods: APOE variants (rs429358; rs7412) were genotyped in 402 POAG patients and 401 controls. We evaluated the association between APOE genetic variants and the risk for POAG, as well as the correlation between the requirement of glaucoma surgery and the APOE polymorphisms. Results: Among the three APOE gene isoforms, we found a low frequency of APOE alleles ε2 (7.34%) and ε4 (11.76%), but a high frequency of ε3 (80.88%) in our population. When compared to ε3ε3 reference genotype, ε2 allele-carriers (OR = 1.516; p-value = 0.04) and ε2ε3 genotype (OR = 1.655; p-value = 0.02) were associated with a greater risk for POAG. An additive genetic model confirmed the influence of the ε2 allele in the risk of POAG in this sample of the Brazilian population (OR = 1.502; p-value = 0.04). There was no significant association between the analyzed genotypes and the requirement or number of glaucoma surgeries (p > .05). Conclusion: Brazilian individuals carrying the APOEε2 allele may be at an increased risk for the development of POAG.

Interleukin-1ß-31 (rs1143627) genetic variant and the risk of age-related macular degeneration in the Brazilian population.

Background: Age-related macular degeneration (AMD) is a multifactorial disease and one of the main causes of blindness in people over 50 years old. The etiology and pathophysiology of AMD are not well understood. The aim of this study was to investigate whether the rs1143627 variant allele of IL1B, which encodes Interleukin (IL)-1ß, a key cytokine, mediates immune and inflammatory responses.Methods: A case-control study was conducted with 397 AMD patients and 402 controls in Brazil. IL1B genotyping was carried out with TaqMan® genotyping assay. Differences in IL1B allele frequencies and genotypes were evaluated between patients and controls and between wet and dry subgroups of AMD. Relationships between allele presence/genotype and disease risk are reported as odds ratios (ORs) with 95% confidence intervals (CIs).Results: Genotype proportions for the rs1143627 variant allele of IL1B were similar between AMD patients and controls (p = .21), with 84.38% of AMD patients and 79.60% of the controls carrying the variant allele. We observed a trend toward the variant allele being associated with AMD risk (OR = 1.38, 95% CI 0.95-2.03, p = .08), as well as a trend toward the variant allele being associated with increased risk for wet AMD in particular (OR = 1.23, 95% CI 0.96-1.56, p = .08).Conclusions: The rs1443627 variant was not associated with AMD risk in this Brazilian population sample. Larger studies are warranted to determine whether the trends observed in this study reflect a relationship between this variant and risk of AMD, especially wet AMD.

Mutation analysis of CRYAA, CRYGC, and CRYGD associated with autosomal dominant congenital cataract in Brazilian families.

PURPOSE: Congenital cataracts are one of the most treatable causes of visual impairment and blindness during infancy. Approximately 50% of all congenital cataract cases may have a genetic cause. Once there is an intimate relationship between crystallin genes and lens transparency, they are excellent candidate genes for inherited cataract. The purpose of this study was to investigate mutations in alphaA-crystallin (CRYAA), gammaC-crystallin (CRYGC), and gammaD-crystallin (CRYGD) in Brazilian families with nuclear and lamellar autosomal dominant congenital cataract. METHODS: Eleven Brazilian families were referred to the Santa Casa de São Paulo Ophthalmology Department. The coding regions and intron/exon boundaries of CRYAA, CRYGC, and CRYGD were amplified by polymerase chain reaction (PCR) and directly sequenced. Mutation screening was performed in the control group by restriction digestion. RESULTS: Two mutations were observed in different families (Family 4 and Family 10), one is a new mutation (Y56X) in CRYGD and the other a previously reported mutation (R12C) in CRYAA that is correlated with a different phenotype. Genetic analysis revealed previously described polymorphisms in CRYAA (D2D) and CRYGD (Y17Y and R95R). A new polymorphism in CRYGC (S119S) was identified only in Family 1. The mutations as well as the new polymorphism were not observed in the control group. CONCLUSIONS: In conclusion, we report a novel nonsense mutation (Y56X) in CRYGD and a previously reported missense mutation (R12C) in CRYAA associated with nuclear cataract in Brazilian families. Both tyrosine in amino acid 56 in CRYGD and arginine in amino acid 12 in CRYAA have been highly conserved throughout evolution in different species. A new polymorphism (S119S) in CRYGC was also observed in one family. The analysis of nine families excluded possible mutations in the crystallin genes, suggesting that other genes could be involved with congenital cataract.