Análise do polimorfismo no gene CYP24A1 em pacientes com dermatite atópica

Abstract

Recent studies have shown that vitamin D (VD) plays an important role in the development of allergic diseases, especially in atopic dermatitis (AD). Calcitriol, a bioactive form of VD, is metabolized endogenously in keratinocytes and lymphocytes by enzymes encoded by CYP27B1 and CYP24A1 genes, involved respectively in their synthesis and inactivation.. Polymorphisms in the CYP24A1 gene (rs2248359) are associated with decreased VD receptor (VDR) activity, which may interfere with the different functions of this vitamin. The aim of this study was to evaluate the frequency of rs2248359 in children and adults with AD and verify its association with the clinical severity of the disease. The distribution of frequencies for categorical variables and medians, means and standard deviations for continuous variables were calculated.. Associations between rs2248359 and the other variables were evaluated using the chi-square test by Odds Ratio (OR) and their respective 95% confidence intervals (95% CI). The standard level of significance 0.05 was used. The study was carried out at the Allergy and Immunology outpatient clinic of State University of Rio de Janeiro (UERJ). Socio-demographic and clinical variables (presence of family history of atopy, rhinitis, asthma) were collected by self-filling questionnaires. The severity of the disease was assessed by Scoring Atopic Dermatitis (SCORAD). Blood samples were collected for DNA extraction, and CYP24A1 genotyping was performed by real-time Polymerase chain reaction (PCR). The control group consisted of adult bone marrow donors enrolled in the Blood Bank of Pedro Ernesto University Hospital UERJ. From November 2015 to June 2018, 48 patients (46% female) and 83 controls (40% female) were evaluated. The distribution of the genotypic and allelic frequencies of CYP24A1 did not differ between the study groups, as well as the ethnicity of the participants. Likewise, there was no statistically significant difference in the frequency of polymorphism between patients with severe/moderate vs mild SCORAD [OR= 0,47; CI95%:0,14 1,54; p=0,24]. On the other hand, CYP24A1 polymorphism was significantly more frequent in females [OR=11,24;CI95%:2,76-45,6;p<0,01], this finding was independent of the others study variables and restricted to the patients group. This study represents a pioneering work on the association of polymorphisms of the CYP24A1 gene and atopic dermatitis in our country. Studies with larger sample size will contribute to a better understanding of the profile of AD-associated polymorphisms in a highly mixed-race population as the brazilian.