Search

• FOXP3 polymorphisms were associated with asthma and atopy in our population. • Gene-environment interactions with EBV were also observed for atopy risk. • The CACNA1F gene was downregulated by rs2280883 (allele C) on lung and whole blood. Polymorphisms in genes related to the activation and development of regulatory T cells (Tregs), such as FOXP3 , may be associated with asthma and atopy development. Additionally, environmental factors such as exposure to infections can modify the effect of these associations. This study evaluated the impact of polymorphisms in the FOXP3 on the risk of asthma and atopy as also gene-environment interactions in these outcomes. This study included 1,246 children from the SCAALA program, between 4 and 11 years of age. DNA was extracted from peripheral blood and eight SNPs (rs2280883, rs11465476, rs11465472, rs2232368, rs3761549, rs3761548, rs2232365 and rs2294021) were genotyped using the 2.5 HumanOmni Beadchip from Illumina (San Diego, California, USA) or TaqMan qRT-PCR. The rs2232368 (Allele T) was positively associated with asthma symptoms (OR = 1.95, CI = 1.04 to 3.66, p = 0.040) and skin prick test (SPT) reactivity to aeroallergens (OR = 2.31, CI = 1.16 to 4.59, p = 0.017). The rs3761549 (Allele T) was positively associated with SPT reactivity (OR = 1.44, CI = 1.03 to 2.02, p = 0.034). The rs2280883 (Allele C) was negatively associated with specific IgE to aeroallergens (OR = 0.83, CI = 0.70 to 0.99, p = 0.040). Furthermore, the rs2280883 played a protective role in the development of atopy only in individuals seropositive to Epstein-Barr virus (EBV) infection (OR = 0.74, CI = 0.60 to 0.92, p = 0.003 and OR = 0.74; 95% CI = 0.61–0.91, p = 0.007 for SPT and slgE respectively), but not in individuals without EBV infection. Polymorphisms in the FOXP3 gene were associated with the risk of atopy and asthma development in our population. In addition, EBV infection had an effect modifier of the observed association for rs2280883 variant. [ABSTRACT FROM AUTHOR]

Background Helicobacter pylori infection is a strong risk factor for gastric cancer, likely due to the extensive inflammation in the stomach mucosa caused by these bacteria. Many studies have reported an association between IL10 polymorphisms, the risk of gastric cancer, and IL-10 production. The aim of the study was to evaluate the association between IL10 genetic variants, Helicobacter pylori infection, and IL-10 production by peripheral blood leukocytes in children. Materials and Methods We genotyped a total of 12 single nucleotide polymorphisms in IL10 in 1259 children aged 4-11 years living in a poor urban area in Salvador, Brazil, using TaqMan probe based, 5′ nuclease assay minor groove binder chemistry. Association tests were performed by logistic regression for Helicobacter pylori infection and linear regression for IL-10 spontaneous production (whole-blood cultures) including sex, age, and principal components for informative ancestry markers as covariates, using PLINK. Results Our results shown that IL10 single nucleotide polymorphisms rs1800896 ( OR = 1.63; 95% CI = 1.11-2.39), rs3024491 ( OR = 1.71; 95% CI = 1.14-2.57), rs1878672 ( OR = 1.79; 95% CI = 1.19-2.68), and rs3024496 ( OR = 1.48; 95% CI = 1.05-2.08) were positively associated with Helicobacter pylori infection. Eight single nucleotide polymorphisms were associated with spontaneous production of IL-10 in culture, of which three (rs1800896 and rs1878672, p = .04; rs3024491, p = .01) were strongly associated with infection by Helicobacter pylori. Conclusions Our results indicate that IL10 variants rs1800896, rs3024491, rs1878672, and rs3024496 are more consistently associated with the presence of anti- H. pylori IgG by inducing increased production of IL-10. Further studies are underway to elucidate the role of additional genetic variants and to investigate their impact on the occurrence of gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract: 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 ≥52years 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 ≥52years (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. [Copyright &y& Elsevier]