RESUMO
A complete screening of the CFTR gene by DGGE and DNA sequencing was performed in patients with sarcoidosis. In 8/26 cases, missense and splicing CFTR gene mutations were found, a significant difference over controls (9/89) from the same population (P = 0.014). The odds ratio for a person with a CFTR gene mutation to develop the disease is 3.95 (1.18 < OR < 13.26). Seven different CFTR gene mutations were observed: R75Q, R347P, 621 + 3 A/G, 1898 + 3 A/G, L997F, G1069R, and a novel mutation which was detected in this study, I991V. R75Q mutation was present in 3/26 patients, a significant increase (P = 0. 01) in cases over controls, indicating its preferential association with sarcoidosis. A trend towards disease progression was observed in patients with CFTR gene mutations compared to patients without mutations. These data suggest that CFTR gene mutations predispose to the development of sarcoidosis.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Frequência do Gene , Mutação , Sarcoidose Pulmonar/genética , Adulto , Processamento Alternativo , Estudos de Casos e Controles , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/fisiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Fenótipo , Isoformas de Proteínas/genética , Sarcoidose Pulmonar/epidemiologiaRESUMO
Desmosine (DES) is an elastin-derived, cross-link amino acid, which is not metabolized; hence, its urinary levels reflect elastin breakdown. We hypothesized that elastin degradation should increase as a result of increased lung inflammation during an acute exacerbation of COPD and should decrease after recovery. To test this hypothesis we measured DES in three urine samples from nine COPD subjects during the first 5 days of an acute exacerbation and at 2 months after recovery. We also measured forced expiratory volume in 1 sec (FEV1) to monitor the effects ofthe exacerbation on ventilatory function. The mean (SD) FEV1 was 45 (15)% predicted during the exacerbation and 57.8 (16)% predicted 2 months later (P=0.00001). The mean (SD) DES excretion was 25.3 (9) microg g(-1) creatinine at day 1;23.5 (9) at day 3 and 24 (9) at day 5 of the exacerbation. The mean (SD) urinary DES excretion 60 days after discharge was 20.9 (7) microg g(-1) creatinine (P=0.049) in comparison with the mean of the three acute-phase values. The size of the increase in desmosine excretion during exacerbation is small, 3.2 microg g(-1) creatinine or 16% of the recovery desmosine value. We conclude that there is a small but statistically significant increase in lung elastin breakdown in the body during an acute exacerbation of COPD.