Cystic fibrosis transmembrane conductance regulator (CFTR) gene
mutations in Asians with chronic pulmonary disease: A pilot studyB
Nicola S.P. Ngiama,b,*, Samuel S. Chonga, Lynette P.C. Sheka,b, Denise L.M. Goha,b,
K.C. Ongc, S.Y. Chngb, G.H. Yeoa, Daniel Y.T. Goha,b
aDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5, Lower Kent Ridge Road, Singapore 119074, Singapore
bChildren’s Medical Institute, National University Hospital, 5, Lower Kent Ridge Road, Singapore 119074, Singapore
cKC Ong Chest and Medical Clinic, 3, Mount Elizabeth, #12-03, Mount Elizabeth Medical Centre, Singapore 228510, Singapore
Received 14 December 2005; received in revised form 19 February 2006; accepted 19 February 2006
Available online 6 March 2006
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 I125Twith idiopathic bronchiectasis alone
suggests that different mutations predispose to different disease.
D 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Keywords: CFTR mutations; Bronchiectasis; Asthma; Asians
The CFTR gene is located on the long arm of
chromosome 7 and consists of 230 kb and contains 27
coding exons. There are more than 1400 CFTR sequence
variations identified in the cystic fibrosis (CF) mutation
database (http://www.genet.sickkids.on.ca/cftr/). The types
and distributions of mutations vary significantly among
different populations [1–3]. The majority of mutations have
been identified in European and North American popula-
tions but the spectrum of mutations and genetic polymor-
phism has not been well described in Chinese and Indians.
Even less is known in Malays.
The association between CFTR mutations and asthma is
controversial. Mennie et al.  did not find any association
between the CFTR gene mutations and asthma in a British
population. Looking at specific mutations, the link between
DF508 heterozygosity and CFTR mutations with asthma has
also been conflicting. Some authors  suggested that
DF508 heterozygosity was associated with an increased
susceptibility to asthma in a Danish population while
Schroeder et al.  suggested that obligate DF508 carriers
are protected from asthma. There is some evidence that
1569-1993/$ - see front matter D 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
iData was presented at the 39th Singapore–Malaysia Congress of
Medicine, 30 June – 3 July, 2005 in Singapore for the Young Investigator’s
* Corresponding author. National University Hospital, Children’s Medical
Institute, 5 Lower Kent Ridge Road, Main Building Level 4, Singapore
119074, Singapore. Tel.: +65 67724420; fax: +65 67797486.
E-mail address: email@example.com (N.S.P. Ngiam).
Journal of Cystic Fibrosis 5 (2006) 159 – 164
 Strong TV, Wilkinson DJ, Mansoura MK, et al. Expression of an
abundant alternatively spliced form of the cystic fibrosis transmem-
brane conductance regulator (CFTR) gene is not associated with a
cAMP-activated chloride conductance. Hum Mol Genet 1993;2:
 Groman JD, Hefferon TW, Casals T, et al. Variation in a repeat
sequence determines whether a common variant of the cystic fibrosis
transmembrane conductance regulator gene is pathogenic or benign.
Am J Hum Genet 2004;74:176–9.
N.S.P. Ngiam et al. / Journal of Cystic Fibrosis 5 (2006) 159–164