PURPOSE: CFTR mutations are well studied in Caucasian populations, but data on the spectrum of mutations and genetic polymorphisms in Asian populations are only just emerging. This study aims to explore the correlation of CFTR mutations with chronic pulmonary disease in the ethnic Chinese population of Singapore.
METHODS: Twenty-nine ethnic Chinese subjects with chronic pulmonary disease were recruited for the study, 15 with severe asthma, 10 with idiopathic bronchiectasis and 1 each with primary ciliary dyskinesia (PCD), bronchiolitis obliterans organizing pneumonia (BOOP), recurrent sinusitis, and recurrent pneumonia. Sweat chloride testing was performed on all subjects, and all 27 exons and flanking intronic sequences of the CFTR gene were screened for mutations. Subjects with elevated sweat chloride or clinical features of cystic fibrosis were excluded. Forty healthy ethnic Chinese subjects with no chronic pulmonary disease or family history of cystic fibrosis were used as controls.
RESULTS: Fourteen subjects with chronic pulmonary disease (48%, p=0.0084) were found to carry a CFTR mutation. They comprised 7 with severe asthma, 4 with idiopathic bronchiectasis and the patients with PCD, BOOP and recurrent sinusitis. Seven subjects in the control group also carried a CFTR mutation. The known CFTR mutations identified were 12TG5T, I125T, I556V and Q1352H, while 2 mutations were novel. The missense mutation I125T was significantly associated with idiopathic bronchiectasis (p=0.02) but was not observed in subjects with severe asthma. In contrast, the I556V and Q1352H mutations were nominally more prevalent in severe asthma subjects compared to controls, while they were not observed in subjects with idiopathic bronchiectasis.
CONCLUSION: The higher frequency of CFTR mutations in ethnic Chinese with chronic pulmonary disease compared to race-matched controls suggests that these mutations may predispose to disease. The significant association of I125T with idiopathic bronchiectasis and nominal association of I556V and Q1352H with severe asthma suggest a possible correlation between mutation and clinical presentation.
CLINICAL IMPLICATIONS: Further studies with larger sample cohorts are necessary to validate these genotype-phenotype observations.
DISCLOSURE: Eugene Han, No Financial Disclosure Information; No Product/Research Disclosure Information