title: Independent contribution of common CFTR variants to chronic pancreatitis.
abstract: OBJECTIVE
  We have assessed whether CFTR gene has a major impact on chronic pancreatitis (CP) pathogenesis than that provided by the CFTR mutations. For this aim, we have evaluated clinical parameters, CFTR mutations, and 3 potential regulatory CFTR variants (coding single-nucleotide polymorphisms): c.1540A>G, c.2694T>G, and c.4521G>A.
  
  
  METHODS
  CFTR gene analysis was performed in a cohort of 136 CP patients and 93 controls from Spanish population using current scanning techniques (single-strand conformation polymorphism/heteroduplex, denaturing gradient gel electrophoresis, and denaturing high-performance liquid chromatography) and direct sequencing.
  
  
  RESULTS
  A higher frequency of CFTR mutations were observed in patients (39%) than in controls (15%; P < or = 0.001), differences being mostly attributable to the prevalence of the cystic fibrosis (CF)-causing mutations (P = 0.009). The analysis of variants has shown statistically significant differences between patients and controls for c.4521G>A (Pcorrected = 0.036). Furthermore, the multi-marker analysis revealed that the 1540A;2694G;4521A (AGA) haplotype was more prevalent in CP than controls (Pcorrected = 0.042). Remarkably, this association was unrelated to CF-causing mutations (P = 0.006).
  
  
  CONCLUSIONS
  Our results corroborate the higher susceptibility of CF carriers to CP and, furthermore, suggest that the AGA haplotype could contribute to an increased risk in the development of CP irrespective of other CF-causing mutations.
authors.affiliation: Genetic Cause of Disease, Genes and Disease Program, Center for Genomic Regulation, Fundació IDIBELL, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cid
authors.forename: Maria D
authors.initials: MD
authors.lastname: Ramos
authors.forename: Luís
authors.initials: L
authors.lastname: Aparisi
authors.forename: Cecilia
authors.initials: C
authors.lastname: García
authors.forename: Josefina
authors.initials: J
authors.lastname: Mora
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Antoni
authors.initials: A
authors.lastname: Farré
authors.forename: Teresa
authors.initials: T
authors.lastname: Casals
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D050500:Pancreatitis, Chronic / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain; D055815:Young Adult
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator