CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity.
BACKGROUND
Cystic fibrosis (CF) lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs) in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease.


METHODS
The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1) > 70% and < 40%).


RESULTS
PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene.


CONCLUSIONS
CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity.
Blaisdell
Carol J
CJ
Department of Genetics, School of Medicine, University of Maryland, Howard Hall 596, 660 W, Redwood St,, Baltimore, Maryland, USA. cblaisdell@peds.umaryland.edu
Howard
Timothy D
TD
Stern
Augustus
A
Bamford
Penelope
P
Bleecker
Eugene R
ER
Stine
O Colin
OC
D000328:Adult; D001483:Base Sequence; D000090007:CLC-2 Chloride Channels; D002460:Cell Line; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008171:Lung Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D012720:Severity of Illness Index
C505032:CFTR protein, human; D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA