Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asians with chronic pulmonary disease: a pilot study.
BACKGROUND
Little is known about the relationship between cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asian patients and severe asthma or idiopathic bronchiectasis. We investigated this potential relationship in the Singaporean Chinese.


METHODS
Twenty patients with chronic pulmonary disease, 14 with severe asthma and 6 with idiopathic bronchiectasis, were screened for CFTR mutations by direct gene sequencing. The frequencies of identified putative mutations were compared against 40 unaffected controls and 96 unselected population samples.


RESULTS
Three missense mutations (I125T, I556V, and Q1352H) and 1 splice site variant (intron 8 12TG5T) were identified in a total of 10 patients, representing a combined mutant/variant allele frequency of 0.25. These alleles were also observed in the controls, but at a significantly lower allele frequency of 0.09 (P<0.01). Furthermore, the I125T mutation was significantly associated with the idiopathic bronchiectasis sub-group (P<0.05).


CONCLUSIONS
The significantly higher frequency of CFTR mutations among patients with chronic pulmonary disease compared with unaffected controls suggests that these mutations may increase risk for disease. The association of I125T with idiopathic bronchiectasis alone suggests that different mutations predispose to different disease.
Ngiam
Nicola S P
NS
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5, Lower Kent Ridge Road, Singapore 119074, Singapore. paensp@nus.edu.sg <paensp@nus.edu.sg>
Chong
Samuel S
SS
Shek
Lynette P C
LP
Goh
Denise L M
DL
Ong
K C
KC
Chng
S Y
SY
Yeo
G H
GH
Goh
Daniel Y T
DY