Estudo de associação de variantes do gene BDNF com fenótipos de asma e atopia em uma população brasileira

Abstract

Asthma is one of the most common noncommunicable diseases in the world, affecting from 1 to 29% of the population in different countries. The inflammatory process of asthma is associated with immune system activation, airway hyperresponsiveness, epithelial cell activation, mucus overproduction, and airway remodeling. It is well recognized that Th2 cells are the main drivers of eosinophilic allergic airway inflammation, generating abundant amounts of IL-4, IL-5, IL-9 and IL-13. However, asthma in adults is more often non-allergic than allergic. Although inflammation appears as a key feature of the exacerbated response in asthma, anti-inflammatory therapy only reduces this exaggerated response but is not able to suppress it, leading to the hypothesis that other factors besides the inflammatory process contribute to the symptoms. observed in asthma. Barrier tissues, such as the lungs, are innervated by the peripheral nervous system, which detects stimuli, including harmful ones, and responds to them by regulating autonomic reactions. The nervous system in the tract plays an important role in regulating mucus intensity, vascular permeability, airway smooth muscle tone, and blood flow. Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin present in the lower airways and may contribute to changes in the structure and function of the airways. Individuals with asthma were selected from the patient cohort of the Program for Asthma Control in Bahia (ProAR). Peripheral blood samples were collected for cell counting, laboratory tests and DNA removal. Serum was stored for subsequent IgE and specific cytokine assays. All subjects underwent skin prick testing (SPT) for common allergies. The objective of this research was to evaluate the impact of variants in the BDNF gene on asthma and atopy phenotypes. The results showed that the G allele of rs962369 was associated with asthma levels (OR 0.74, 95% CI 0.564-0.985, p= 0.038). The A, G, G, G, T and A alleles of rs6265, rs11030104, rs7103411, rs988748, rs10767664, rs2030323, respectively, were specific associated with lack of reversibility. The G allele of SNVs rs7124442 was significantly associated with lower odds of atopy (OR 0.75, 95% CI 0.575-0.989, p= 0.041). While the G allele of SNV rs2030324 and the A allele of rs7934165 were associated with a greater chance of atopy (OR 1.26, 95% CI 1.048-1.516, p= 0.014) and (OR 1.25, 95% CI 1.041 - 1.506, p = 0.016). The G allele of rs7124442 and the A allele of rs11030119 were associated with a greater chance of exacerbation (OR = 1.575, Pperm = 0.037 and OR = 1.823, Pperm = 0.029). Furthermore, the G allele of the rs7124442 SNVs was associated with reduced IL-5 and IgE levels and associated with increased neutrophils in the blood. These data show that variants of the BDNF gene have an impact on asthma and also on atopy in our population.