Genetic polymorphism (rs6587666) in FLG protects from eczema in admixed Brazilian children population with high African ancestry.

Genetic variants in filaggrin (FLG) are key in eczema and are less common in Africans than in Europeans and Asians. Here we examined the association between FLG Single Nucleotide Polymorphisms (SNPs) and eczema in a population of admixed Brazilian children and whether African ancestry modifies this association. We included 1010 controls and 137 cases and ran logistic regressions between SNPs in FLG and eczema in the studied population and also stratified the analyses according to the degree of African ancestry. In addition, we tested the replication of the findings on an independent set of individuals, as well as, we verified the impact on FLG expression according to each SNP genotype. The T allele of SNP rs6587666 was negatively associated with eczema in additive model (OR: 0.66, 95% CI: 0.47-0.93, P: 0.017). Moreover, African ancestry modifies the association between rs6587666 and eczema. The effect of the T allele was higher among individuals with higher African ancestry and the association with eczema was lost in individuals with lower African ancestry. In our analyses the expression of FLG in skin was slightly downregulated by the presence of the T allele of rs6587666. In our population, the T allele of rs6587666 in FLG was associated with protection to eczema and the degree of African ancestry was able to modify the observed association.

The correlation between ancestry and color in two cities of Northeast Brazil with contrasting ethnic compositions.

The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of 'race' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3-5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry.

Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population.

The present study aimed to investigate the association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with primary open angle glaucoma (POAG). We conducted a case-control study that included 90 patients with POAG and 127 healthy controls whose blood samples were genotyped for the functional polymorphisms T-786C and Glu298Asp of the eNOS gene by Taqman fluorescent allelic discrimination assay. The T-786C polymorphism was significantly associated as a risk factor for POAG among women (OR: 2.28; 95% CI: 1.11 to 4.70, p=0.024) and marginally associated to the risk of POAG in the patients ≥52 years of age at diagnosis (OR: 2.11; 95% CI: 0.98 to 4.55, p=0,055). However, these results was not confirmed after adjustments for gender, age, self-declared skin color, tobacco smoking and eNOS genotypes by multivariate logistic regression model (OR: 2.08; 95% CI: 0.87 to 5.01, p=0.101 and OR: 2.20; 95% CI: 0.95 to 5.12, p=0.067, respectively). The haplotype CG of T-786C and Glu298Asp showed a borderline association with risk of POAG in the overall analysis (OR: 1.76; 95% CI: 0.98 to 3.14, p=0.055) and among women (OR: 2.02; 95% CI: 0.98 to 4.16, p=0.052). Furthermore, the CG haplotype was significantly associated with the development of POAG for the age at diagnosis group ≥52 years (OR: 3.48; 95% CI: 1.54 to 7.84, p=0.002).We suggested that haplotypes of the polymorphisms T-786C and Glu298Asp of eNOS may interact with gender and age in modulating the risk of POAG.

Is the GSTM1 null polymorphism a risk factor in primary open angle glaucoma?

PURPOSE: To investigate the association of glutathione S-transferase (GST) GSTM1, GSTT1, and GSTP1 genes with the risk of primary open angle glaucoma (POAG) and clinical features of the disease. METHODS: We conducted a case-control study that included 87 Brazilian patients with POAG and 85 healthy controls matched for age, ethnicity, and sex, whose blood samples were genotyped for polymorphisms in GST genes using polymerase chain reaction (PCR) based methods. RESULTS: The GSTM1 null polymorphism was significantly more common in the POAG than in the controls group (OR: 2.1, 95% CI: 1.13-3.9; p=0.018). The combined GSTM1 null/GSTT1+ genotype and GSTM1 null/GSTP1 Ile/Val or Val/Val was more prevalent in POAG patients, being a risk factor for POAG (OR: 2.4, 95% CI: 1.16-4.9; p=0.016 and OR: 2.7, 95% CI: 1.07-6.74; p=0.033, respectively). The GSTM1 null/GSTT1+ genotype were associated with higher levels of IOP of both eyes and with more severe defect of the right eye optic nerve. The GSTM1 null/GSTP1 Ile/Val or Val/Val genotypes were associated with higher levels of IOP and more advanced defect of the right eye optic nerve and visual field. CONCLUSIONS: We demonstrate that GSTM1 null polymorphism is associated with POAG in the Brazilian population.