Polyvariant mutant CFTR genes in patients with chronic pancreatitis

Several authors have reported an association between mutations of the cystic fibrosis transmembrane conductance regulator gene (CFTR) and chronic pancreatitis. CFTR gene transcription and protein efficiency are influenced by two polymorphic loci, (TG)m and M470V, other than the T5 allele, whose role is already well-established. The TG11/T5 haplotype is commonly found in healthy subjects, while the TG12/T5/V470 and TG13/T5/V470 haplotypes are present in congenital bilateral absence of the vas deferens (CBAVD) patients. While the T5 allele is a mutation that is over-represented in patients with chronic pancreatitis, no data are available concerning the possible allelic preference at the other two polymorphic loci, (TG)m and M470V, in these patients. For this reason, we screened 39 patients with chronic pancreatitis for the most common CFTR mutations found so far in the Italian population; in addition, we examined the length of the polypyrimidine (poly-T) tract in intron 8, the (TG)m length and the M or V codon at position 470. CFTR mutations were found in 3 patients. Poly-T variant typing identified genotype T5/T7 in 5 patients and T5/T9 in 1 patient. Direct sequencing of intron 8 in patients with the T5 variant revealed the TG12/T5/V470//TG11/T7/V470 genotype in 5 patients and TG10/T9//TG11,T5 genotype in 1 patient. In patients with chronic pancreatitis, the T5 allele is frequently associated with TG12 and V470, a haplotype already reported in CBAVD cases and quite uncommon in healthy subjects.