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A haplotype-based molecular analysis of CFTR mutations associated with respiratory and pancreatic diseases

 Ji Hyun Lee  ;  Ji Ha Choi  ;  Min Goo Lee  ;  Kyung Hwan Kim  ;  Jong-Eun Lee  ;  Mi-Ook Cho  ;  Sung Joon Kim  ;  Joo Hyun Nam  ;  In-Jin Jang  ;  Yousin Suh  ;  Joo-Heon Yoon  ;  Dong Soo Kim  ;  Seung Woo Park  ;  Si Young Song  ;  Joon Chang  ;  John W. Hanrahan  ;  Wan Namkung 
 HUMAN MOLECULAR GENETICS, Vol.12(18) : 2321-2332, 2003 
Journal Title
Issue Date
Alleles ; Animals ; Bicarbonates/metabolism ; Bronchiectasis/genetics ; CHO Cells ; Case-Control Studies ; Chloride Channels ; Chlorides/metabolism ; Cricetinae ; Cricetulus ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; DNA Mutational Analysis ; Evolution, Molecular ; Gene Frequency ; Genetic Variation ; Haplotypes* ; Humans ; Ion Transport ; Korea ; Microsatellite Repeats ; Mutagenesis, Site-Directed ; Mutation* ; Pancreatic Diseases/genetics* ; Pancreatitis/genetics ; Polymorphism, Genetic ; Respiratory System/physiopathology*
the CFTR gene in the Korean population. Individual variants at these sites were analyzed by conventional DNA screening in 117 control and 75 patients having bronchiectasis or chronic pancreatitis. In a haplotype determination based on a Bayesian algorithm, 15 haplotypes were assembled in the 192 individuals tested. Several haplotypes, especially with Q1352H, IVS8 T5, and E217G, were found to have disease associations in a case-control study. Notably, a common polymorphism of M470V appears to affect the intensity of the disease association. Among the two haplotypes having IVS8 T5, the T5-V470 haplotype showed higher disease association than the T5-M470 haplotype. In addition, a Q1352H mutation found in a V470 background showed the strongest disease association. The physiological significances of the identified mutations were rigorously analyzed. Non-synonymous E217G and Q1352H mutations in the M470 background caused a 60-80% reduction in CFTR-dependent Cl(-) currents and HCO3(-) -transport activities. Surprisingly, the additional M470V polymorphic variant with the Q1352H mutation completely abolished CFTR-dependent anion transport activities. These findings provide the first evidence on the importance of CFTR mutations in the Asian population. Importantly, the results also reveal that interactions between multiple genetic variants in cis affect the final function of the gene products.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Kim, Dong Soo(김동수)
Park, Seung Woo(박승우) ORCID logo https://orcid.org/0000-0001-8230-964X
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
Yoon, Joo Heon(윤주헌)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Lee, Ji Hyun(이지현)
Chang, Joon(장준) ORCID logo https://orcid.org/0000-0003-4542-6841
Choi, Ji Ha(최지하)
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