Associação de variantes genéticas nos genes DAD1 e OXA1L com asma e atopia em uma população adulta

Abstract

Asthma is a highly complex immune-mediated disease, characterized by a reversible and intermittent obstruction of the airways that, despite having a higher prevalence in childhood, has shown a high incidence and mortality in adults. In recent years, several genomic wide association studies (GWAS) have identified a significant number of genetic variants responsible for asthma susceptibility. These variants have been shown to play an important role in the regulation of gene expression and in the heritability of asthma, including variants in DAD1 e OXA1L genes. The DAD1 gene is known for its role in the regulation of programmed cell death, and OXA1L is described for its involvement in mitochondrial biogenesis and oxidative phosphorylation. The present study aimed to identify new variants in the DAD1 and OXA1L genes and to evaluate the association with asthma and atopy markers in adults. The study involved the participation of 1,084 adult individuals divided into mild to moderate asthma, severe asthma and healthy controls belonging to a case-control study cohort of the Programa para Controle da Asma na Bahia-ProAR. Analyzes of associations between variants in the studied genes and asthma or atopy were performed using a multivariate logistic regression model adjusted for sex, age, body mass index (BMI), smoking, forced expiratory volume in 1 second (FEV1) and ancestry (PC1) using PLINK 1.9 software. Additive, dominant and recessive genetic models were used for all analyzed variables. In this study, new variants in the DAD1 and OXA1L genes that had never been described before were identified. The C allele of rs200470407 in OXA1L was negatively associated with lack of asthma control and increased IL-13. The A allele of rs61972400 and the C allele of rs76050305 in DAD1 were positively associated with airway obstruction, in addition to being in total linkage disequilibrium. In silico gene expression analyzes demonstrated that some of the polymorphisms in both genes are able to affect their respective levels of gene expression. Thus, our findings demonstrate that variants in the DAD1 and OXA1L genes may influence asthma and atopy in Brazilian adults.