Polymorphisms in the DAD1 and OXA1L genes are associated with asthma and atopy in a South American population

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-16T11:49:50Z No. of bitstreams: 1 Pires AO Polymorphisms in the DAD1 and OXA1L....pdf: 1226142 bytes, checksum: c0fa5af323611b005d0a4abe202c2c33 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-16T11:59:43Z (GMT) No. of bitstreams: 1 Pires AO Polymorphisms in the DAD1 and OXA1L....pdf: 1226142 bytes, checksum: c0fa5af323611b005d0a4abe202c2c33 (MD5)Made available in DSpace on 2018-08-16T11:59:43Z (GMT). No. of bitstreams: 1 Pires AO Polymorphisms in the DAD1 and OXA1L....pdf: 1226142 bytes, checksum: c0fa5af323611b005d0a4abe202c2c33 (MD5) Previous issue date: 2018Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB).Federal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Allergy and Acarology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilAtopic asthma, which is characterized by the chronic inflammation and morbidity of airways, is a disease of great complexity, and multiple genetic and environmental factors are involved in its etiology. In the first genome-wide association study (GWAS) conducted in Brazil for asthma, a positive association was found between atopic asthma and a variant (rs1999071), which is located between the DAD1 and OXA1L genes, although neither gene has previously been reported to be associated with asthma or allergies. The DAD1 gene is involved in the regulation of programmed cell death, and OXA1L is involved in biogenesis and mitochondrial oxidative phosphorylation. This study aimed to evaluate how polymorphisms in DAD1 and OXA1L are associated with asthma and markers of atopy in individuals from the Salvador cohort of the SCAALA (Social Change Asthma and Allergy in Latin America) program. The DNA of 1220 individuals was genotyped using the Illumina 2.5 Human Omni Bead chip. Logistic regression analyses were performed with PLINK 1.9 software to verify the association between DAD1 and OXA1L polymorphisms and asthma and atopic markers, adjusted for sex, age, helminth infections and ancestry markers, using an additive model. The DAD1 and OXA1L genes were associated with some of the evaluated phenotypes, such as asthma, skin prick test (SPT), specific IgE for aeroallergens, and Th1/Th2-type cytokine production. Using qPCR, as well as in silico gene expression analysis, we have demonstrated that some of the polymorphisms in both genes are able to affect their respective gene expression levels. In addition, DAD1 was over-expressed in asthmatic patients when compared with controls. Thus, our findings demonstrate that variants in both the DAD1 and OXA1L genes may affect atopy and asthma in a Latin American population with a high prevalence of asthma