Avaliação genética nos diferentes fenótipos da Doença Pulmonar Obstrutiva Crônica

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by heterogeneous presentation and recently, patients have been divided into different phenotypes : Exacerbator, Mixed COPD-asthma and Emphysema hyperinflation. Several genes have been evaluated for possible relationship with COPD; however, polymorphisms associated with five of these genes have shown more significant results: EPHX1, GSTP, CHRNA3 / 5, HHIP and FAM 13A. The study evaluated the presence of genetic polymorphisms in the three different phenotypes described above. Recently, some genetic polymorphisms have been implicated as probable genetic factors that would increase the susceptibility to the development of COPD but without association with different phenotypes. The main objective of the study was to correlate genetic polymorphisms associated with COPD with the different clinical phenotypes of the disease. Secondary objectives included assessing the presence of the major genetic polymorphisms described in the literature despite the patients phenotype, as well as trying to establish their correlation with COPD severity and smoking habit and to compare the presence of genetic polymorphisms between COPD group and smokers without airflow obstruction. Observational study that analysed the above variables in COPD patients with the three different phenotypes, and compared it with a control group of healthy individuals and another of smokers without airflow obstruction. The control group consisted of 42 individuals, the smoker by 29 individuals. The COPD group consisted of 94 patients, 26 of which were emphysema hyperinsuflation, 14 mixed asthma / COPD, 21 exacerbators and 33 patients who did not fit all the phenotypes and / or did not complete all the exams. After signing the informed consent, the patients were submitted to clinical questionnaire, spirometry and serum exams with blood count cells evaluation and genetic polymorphisms by real-time PCR and, subsequently, genetic sequencing technique. The COPD group patients underwent pulmonary volume and CO diffusion measurements. After analysing the data related to the main objective of the study, a statistically significant difference between COPD phenotypes was identified when the rs 13118928 polymorphism. The presence of allele A is possibly related to the tendency to develop emphysema / hyperinflation phenotype and the presence of G allele is possibly unrelated to this phenotype. When analyzing secondary objectives, we observed a statistically significant difference in both polymorphisms of the CHRNA3 / 5 gene regarding predisposition to cigarette addiction and in the rs2234922 polymorphism of the EPHX1 gene regarding the possibility of predisposing to COPD. In the analysis of single variables considering only COPD patients, we observe a statistically significant in TPC% in two different polymorphisms of HHIP gene. In the analysis of the absolute number of serum eosinophils we observed a statistically significant difference in the rs1829541 polymorphism of the HHIP gene. This paper points to the need for further studies on the topic, which will be important for a better understanding and management of COPD.