Analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, in patients with alcoholic liver disease (ALD) and alcoholic chronic pancreatitis (ACP)
Abstract
Introduction: Cystic fibrosis (CF) is an autosomal recessive disorder affecting multiple organs. A defective CFTR gene leads to inadequate transport of Cl ions between intra- and extracellular environment of cells in affected organs. Susceptibility to alcoholic chronic pancreatitis (ACP) could be genetically determined. Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) genes have been variably associated with both hereditary and idiopathic form of chronic pancreatitis (CP). Our aim was to analyze these genes in ACP patients. Mutational screening was performed in 05 unrelated ACP patients and 05 patients with alcoholic liver disease (ALD).
Method: Patients with ACP and ALD, were admitted in Bundelkhand Medical College hospital, Sagar, and enrolled for genetic analysis. Genomic DNA was extracted from whole blood according to the established protocols using the DNA Isolation Kit for Mammalian blood (Genei Bangalore).
Results: Mutation analysis of CFTR was performed in all ACP and ALD patients. In three ACP patients, ΔF508 mutation was detected in heterozygous state with a prevalence rate of 8.88%. R117 H was another mutation detected in ACP patients in heterozygous state.
Conclusion: Present study was performed to determine whether patients with ACP and ALD had mutations in the CFTR gene and to explore whether non coding sequences that produce low levels of CFTR mRNA (the 5T allele) was responsible for above mentioned abnormalities. Our hypothesis was that the pancreatic damage due to high alcohol intake could be due to abnormal allele or a combination of multiple mutations occurring in the two alleles in CFTR gene.
Downloads
References
2. Anderson, D.H. (1938) Cystic fibrosis of the pancreas and its relation to celiac disease: A clinical and pathological study. Am. J. Dis. Child 56, 344-349. [PubMed]
3. Williams SG, Westaby D, Tanner MS, Mowat AP. Liver and biliary problems in cystic fibrosis. Br Med Bull. 1992 Oct;48(4):877-92. [PubMed]
4. C.F.F. (2003, 2004,2006) Cystic Fibrosis Foundation Patient registry. Annual Data Report. Toronto, Canada. [PubMed]
5. Sharer N, Schwarz M, Malone G, Howarth A, Painter J, Super M, Braganza J. Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. N Engl J Med. 1998 Sep 3;339(10):645-52. [PubMed]
6. Cohn JA, Strong TV, Picciotto MR, Nairn AC, Collins FS, Fitz JG. Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells. Gastroenterology. 1993 Dec;105(6):1857-64. [PubMed]
7. Chillón M, Casals T, Mercier B, Bassas L, Lissens W, Silber S, Romey MC, Ruiz-Romero J, Verlingue C, Claustres M, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med. 1995 Jun 1;332(22):1475-80. [PubMed]
8. Noone PG1, Zhou Z, Silverman LM, Jowell PS, Knowles MR, Cohn JA. Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor genemutations. Gastroenterology. 2001 Dec;121(6):1310-9.
9. Audrézet MP, Chen JM, Le Maréchal C et al: Determination of the relative contribution of three genes, the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene, to the etiology of idiopathic chronic pancreatitis. Eur J Hum Genet 2002; 10: 100–106.
10. Chu CS, Trapnell BC, Curristin S, Cutting GR, Crystal RG. Genetic basis of variable exon 9 skipping in cystic fibrosis transmembrane conductance regulator mRNA. Nat Genet. 1993 Feb;3(2):151-6.
OAI - Open Archives Initiative
