No abstract

Multiple factors interact to trigger allergic diseases, including individual genetic background and factors related to the environment such as exposure to allergens, air pollution and respiratory infections. The FOXP3 transcription factor is constitutively expressed in CD4+CD25+FOXP3+ regulatory T cells (Tregs) and is critical for the maintenance of immune homeostasis. For example, FOXP3 is responsible for the suppression of the Th2 response following exposure to allergens. Studies have shown that expression of the FOXP3 gene is reduced in patients with asthma and allergies compared to healthy controls. Therefore, the impairment of FOXP3 function caused by genetic polymorphisms and/or epigenetic mechanisms may be involved in the etiology of asthma and other allergic diseases. This review discusses some aspects of the role of FOXP3 in the development of asthma and allergy, with a particular emphasis on genetic and epigenetic factors.

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.

Objectives: This observational study analyzed telomerase reverse transcriptase (pTERT) mutations in 45 fine-needle aspiration (FNA) specimens obtained from thyroid nodules followed by postoperatively confirmation of papillary thyroid cancer (PTC) diagnosis, examining their relationship with clinicopathologic aspects and the BRAF V600E mutation. Subjects and methods: Clinical information was collected from patients who presented to Ribeirao Preto University Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between January 2010 to October 2012. Tests included a DNA-based somatic detection of BRAF V600E and pTERT mutations. Results: We found coexistence of pTERT C228T and BRAF V600E mutations in 8.9% (4/45) of thyroid nodules. All nodules positive for pTERT mutations were BRAF V600E positives. There was a significant association between pTERT C228T /BRAF V600E with older age and advanced stage compared with the group negative for either mutation. Conclusions: This series provides evidence that FNA is a reliable method for preoperative diagnosis of high-risk thyroid nodules. pTERT C228T /BRAF V600E mutations could be a marker of poor prognosis. Its use as a personalized molecular medicine tool to individualize treatment decisions and follow-up design needs to be further studied.

Exposure to different organisms (bacteria, mold, virus, protozoan, helminths, among others) can induce epigenetic changes affecting the modulation of immune responses and consequently increasing the susceptibility to inflammatory diseases. Epigenomic regulatory features are highly affected during embryonic development and are responsible for the expression or repression of different genes associated with cell development and targeting/conducting immune responses. The well-known, “window of opportunity” that includes maternal and post-natal environmental exposures, which include maternal infections, microbiota, diet, drugs, and pollutant exposures are of fundamental importance to immune modulation and these events are almost always accompanied by epigenetic changes. Recently, it has been shown that these alterations could be involved in both risk and protection of allergic diseases through mechanisms, such as DNA methylation and histone modifications, which can enhance Th2 responses and maintain memory Th2 cells or decrease Treg cells differentiation. In addition, epigenetic changes may differ according to the microbial agent involved and may even influence different asthma or allergy phenotypes. In this review, we discuss how exposure to different organisms, including bacteria, viruses, and helminths can lead to epigenetic modulations and how this correlates with allergic diseases considering different genetic backgrounds of several ancestral populations.

Several genome-wide association studies have been conducted to investigate the influence of genetic polymorphisms in the development of allergic diseases, but few of them have included the X chromosome. The aim of present study was to perform an X chromosome-wide association study (X-WAS) for asthma symptoms. The study included 1307 children of which 294 were asthma cases. DNA was genotyped using 2.5 HumanOmni Beadchip from Illumina. Statistical analyses were performed in PLINK 1.9, MACH 1.0 and Minimac2. The variant rs12007907 (g.29483892C4A) in IL1RAPL gene was suggestively associated with asthma symptoms in discovery set (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.37-0.67; P = 3.33 × 10 −6 ). This result was replicated in the ProAr cohort in men only (OR = 0.45, 95% CI: 0.21-0.95; P = 0.038). Furthermore, investigating the functional role of the rs12007907 on the production a Th2-type cytokine, IL-13, we found a negative association between the minor allele A with IL-13 production in the discovery set (P = 0.044). Gene-based analysis revealed that NUDT10 was the most consistently associated with asthma symptoms in discovery sample. In conclusion, the rs12007907 variant in IL1RAPL gene was negatively associated with asthma and IL-13 production in our study and a sex-specific association was observed in one of the validation samples. It suggests an effect on asthma susceptibility and may explain differences in severe asthma frequency between women and men.

No abstract

Background and Aim The relationship between race/ethnicity and H pylori infection has been extensively reported, with a higher prevalence of infection observed in black individuals. Whether such differences are due to genetic factors underlying African ancestry remains to be clarified. In the present study, we evaluated the association between the proportion of individual African ancestry and H pylori infection in a sample of 1046 children living in a large Latin American urban center. Materials and Methods Estimation of individual biogeographical ancestry was based on 370,539 SNPs and performed using the ADMIXTURE software. Multivariate logistic regression models and mediation analysis considering the influence of previously recognized socioenvironmental risk factors to H pylori infection were performed. All analyses were conducted using the statistical package STATA v.14.0. Results Each 10% increase in the proportion of individual African ancestry was positively and independently associated with H pylori infection in our population (adjusted OR = 1.22, 95% CI = 1.10‐1.36, P < .001). Mediation analysis demonstrated that only 9.23% of the effect of the individual African ancestry on H pylori infection was explained by factors such as household income, the absence of street paving and crowding. Conclusions The results suggest that genetic variants that covariate with African ancestry may explain an important part of the racial differences observed for the prevalence of H pylori infection.