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Título

VARIANTS OF THE RORA GENE ARE ASSOCIATED WITH ASTHMA IN A SALVADOR POPULATION

Resumo

Introduction: Asthma is a chronic inflammatory disease and is a heterogeneous condition determined by interactions between genetic and environmental factors. The type 2 immune response in asthma triggered by ILC2 can lead to increased eosinophilia and consequent severity of asthma symptoms due to the production of IL-4, IL-5, and IL-13. These cells require ROR-alpha, a specific transcription factor. This study aimed to investigate genetic variants in the RORA gene associated with asthma phenotypes in Salvador - BA. Methods: Whole blood was collected from 1,094 patients from the Programa para Controle da Asma na Bahia (ProAR), DNA was extracted with the FlexiGene kit (Qiagen), mRNA was extracted with the PureLink kit (Thermo Fisher) and converted into cDNA using the SuperScript IV Kit (Thermo Fisher). Genotyping was performed with the MEGA chip (Illumina). RT-PCR was performed with the pre-synthesized Taqman® gene expression assay. Cytokines were measured by the multiplex method using the Luminex® system. Dominant and additive logistic regression models were used for association using PLINK 1.9. Comparisons between genotypes were analyzed using Prism 8, and statistical analyzes were performed using SPSS 25. Results: The G alleleof rs75921170 and the C allele of rs76174258 was associated with a risk of pulmonary obstruction (OR = 3.38 and OR = 3.62) and asthma severity (OR = 2.37 and OR = 2.37) and with increased eotaxin and IL-13 in plasma (p = 0.02 and p = 0.03). The A allele of rs61743834 was associated with increased RORA expression in the plasma of individuals with asthma. In addition, it also obtained a risk associated with asthma and severe asthma (OR = 1.84 and OR = 2.57). Conclusion: Our results on the RORA gene may provide answers about its participation in the pathophysiological mechanisms of asthma and help to discover new personalized treatments in the Brazilian population.