Ngiam, N. S., Chong, S. S., Shek, L. P., Goh, D. L., Ong, K. C., Chng, S. Y. et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in Asians with chronic pulmonary disease: a pilot study. J. Cyst. Fibros. 5, 159-164

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5, Lower Kent Ridge Road, Singapore 119074, Singapore. <>
Journal of Cystic Fibrosis (Impact Factor: 3.48). 08/2006; 5(3):159-64. DOI: 10.1016/j.jcf.2006.02.002
Source: PubMed


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.
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.
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).
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.

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    • "CFTR protein without exon-9 results in a protein with no chloride channel activity (Strong et al., 1993). The shorter allele, 5T, is the most common among congenital bilateral absence of vas deferens and asthma patients (Kanavakis et al., 1998; Ngiam et al., 2006). As the polymorphism is triallelic, the genotype T5/T5 is considered as mutant homozygous, 5T/7T & 5T/9T as heterozygous, and 7T/7T, 9T/9T and 9T/7T as wild-type. "
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    ABSTRACT: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene accounts for an autosomal recessive condition called cystic fibrosis (CF). In the Indian subcontinent, CF and its related diseases are under-diagnosed by the medical community due to the poor knowledge of the disease and its confounding diagnosis, and also due to the poor medical facilities available for these patients, thus causing an increased infant mortality rate with a low life expectancy in general. The aim of the study was to document the spectrum and distribution of CFTR mutations in controls, asthma and chronic pancreatitis cases of Northen India. A total of 800 subjects including 400 controls, 250 asthma cases and150 chronic pancreatitis cases were analyzed for 6 mutations (F508del, G542X, G551D, R117H, W1282X, and S549N) and IVS8 Tn polymorphism. Out of 800 subjects, 18% [(Asthma - 24% (n=250), CP - 29.33% (n=150) cases and controls - 9.3% (n=400)] were positive for heterozygous mutation, 0.8% of the (n=250) asthmatic cases (n=250) were homozygous for IVS8 T5 polymorphism while no subjects were found positive for W1282X mutation. T5 polymorphism was more common in asthmatic cases while F508del mutation in chronic pancreatitis cases. The carrier frequency of F508del, G542X, G551D, R117H, S549N and T5 were 0.015, 0.025, 0.02, 0.005, 0.005, and 0.022 respectively. The cumulative carrier frequency was 0.093. CFTR mutations were underestimated in Indian population. The present study will serve in establishment of genetic screening and prenatal setup for Indian population.
    Gene 01/2014; 539(1). DOI:10.1016/j.gene.2014.01.022 · 2.14 Impact Factor
    • "The most common disease associated with CFTR, although incompletely defined is asthma. Till now several studies have been conducted in different populations and revealed interesting but conflicting facts about asthma development and CFTR gene variation, with some studies showing positive association of CFTR with asthma7835–37 and others showing either protective38 or no association39–45. "
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    ABSTRACT: Mutation on both the copies of cystic fibrosis transmembrane conductance regulator (CFTR) gene results in cystic fibrosis (CF), which is a recessively transmitted genetic disorder. It is hypothesized that individuals heterozygous for CFTR gene mutation may develop obstructive pulmonary diseases like asthma. There is great heterogeneity in the phenotypic presentation and severity of CF lung disease. This could be due to genetic or environmental factors. Several modifier genes have been identified which may directly or indirectly interact with CFTR pathway and affect the severity of disease. This review article discusses the information related to the association of CFTR gene mutation with asthma. Association between CFTR gene mutation and asthma is still unclear. Report ranges from studies showing positive or protective association to those showing no association. Therefore, studies with sufficiently large sample size and detailed phenotype are required to define the potential contribution of CFTR in the pathogenesis of asthma.
    The Indian Journal of Medical Research 04/2012; 135(4):469-78. · 1.40 Impact Factor
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    • "Studies to assess the association of CFTR with asthma have been performed in some populations, yet the results are inconclusive as some studies have shown a positive association of CFTR gene mutation with asthma (Dahl et al. 1998; 2005; Lazaro et al. 1999; Tzetis et al. 2001; Ngiam et al. 2006) while others have found either protective (Schroeder et al. 1995) or no association (Mennie et al. 1995; Kauffmann et al. 1998; Lowenfels et al. 1998; De Cid et al. 2001; Munthe-Kaas et al. 2006; Douros et al. 2008; Kim et al. 2010). Very few studies have been conducted on an Asian population in the context of CFTR and asthma (Ngiam et al. 2006; Kim et al. 2010). CFTR is a 230 kb gene located on chromosome 7 encoding a 1480 amino acid polypeptide, named cystic fibrosis transmembrane regulator, which functions as "
    Annals of Human Biology 01/2011; · 1.27 Impact Factor
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