Contributions for unravelling chronic obstructive pulmonary disease trajectory: associations between genetics and clinical measures

• Autor(a) principal: Melro, Hélder Filipe Fernandes
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/21403
• topic: Doenças pulmonares; Polimorfismos genéticos

Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial and heterogeneous disease which impacts differently on patients with similar grades. This suggests that factor others than lung function may affect patients experience of the disease. Patient-reported outcomes (PROs) are a set of measures that allow to assess patients’ self-perception and experience of the disease. Recent studies have reported associations between specific single nucleotide polymorphisms (SNPs) and PROs, however not much is known about these associations and their meanings. Thus, this study had as main objective to explore possible associations between specific genetic variants and clinical measures, including PROs. It also sought to contribute for a characterization of the genotypes from patients with COPD in Portugal. A cross-sectional study was conducted in a total number of 60 patients with COPD. The PROs assessed were: 1) self-reported frequency of exacerbations, 2) dyspnoea with modified Medical Research Council and Borg scales , 3) fatigue with Borg scale, 4) anxiety and depression with Hospital Anxiety and Depression scale; 5) impact of the disease with COPD Assessment Test and 6) health-related quality of life (HRQOL) with St. George Respiratory questionnaire; Additionally, several surrogate outcomes were also assessed i. e., lung function, peripheral muscle strength with digital dynamometer, respiratory muscle strength with the respiratory pressure assessment and functional capacity through the 1 minute and 5 time sit-to-stand. Both oropharyngeal swabs and saliva samples were collected from the patients for genotyping. Significant associations were found between genetic variants and dyspnoea (rs1143634, rs1042717, rs1138272 and rs12504628), fatigue (rs1042714, rs1138272), anxiety (rs1051303, rs1800450 and rs1131620), impact of the disease (rs10461985 and rs11172113) and HRQOL (rs11172113, rs1042713, rs1138272 and rs12504628). Significant associations were also found between genetic variants and lung function (rs1042713, rs1042717, rs5030737), respiratory muscle strength (rs1130866), peripheral muscle strength (rs1042713, rs1042717, rs11172113, rs11556218) and functional capacity (rs12899618, rs11046966 and rs1138272). This was an exploratory study and more investigations are necessary to confirm the results obtained and to explore deeply the associations and interpretations between genetics and COPD trajectory.