Statistics from Altmetric.com
Editor,—In one of two recently published studies which looked at a link between mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and idiopathic pancreatitis,1 2 Cohn et alestimated that 37% of a cohort of 27 patients with idiopathic pancreatitis had at least one abnormal CFTR gene, which is 11 times the expected frequency.1 Furthermore, the authors concluded that additional CFTR mutations might be detected by more comprehensive DNA testing, because they had tested DNA samples for only 16 of the more than 800 mutations associated with cystic fibrosis.
In order to document further whether a proportion of adults presenting with idiopathic pancreatitis carry alleles linked to mild abnormalities of CFTR functions, we conducted a complete scan of CFTR sequences by denaturing gradient gel electrophoresis (27 exons) and other appropriate methods (four intronic regions), in a sample of 10 patients with isolated idiopathic pancreatitis (ascertained by standard criteria) in the south of France. As some CFTR alleles of specific DNA marker haplotypes have recently been shown to produce incomplete or less functional CFTR protein,3 we also thoroughly studied the TGn-Tn loci in the branch/acceptor splice site in intron 8 and the 1540A/G locus (named M470V) in exon 10. Exclusion criteria included the ingestion of more than two alcoholic drinks per day (20 g ethanol), cancer, drug or trauma related pancreatitis, and familial chronic pancreatitis. None of the patients had any clinical manifestation or family history suggestive of cystic fibrosis or CFTR associated diseases. The study was approved by our ethics committee.
Table 1 summarises the CFTR genotypes identified in the 10 patients with idiopathic pancreatitis. Of these, no patient had a cystic fibrosis mutation and seven were instead heterozygous for one or two sequence changes that have been classified as DNA sequence polymorphisms/variations (a complete list of these variations can be found on the cystic fibrosis mutation database: www.genet. sickkids.on.ca/cftr).
Although variant 1716G/A (no change at glutamine 528) may result in exon 10 skipping and has been reported in CFTR related diseases,4 5 the involvement of this variant in cystic fibrosis remains controversial. The frequency of the IVS8–5T allele (10%) was 2.3 times the observed frequency in the general population (4.3%). It is unlikely, however, that this allele is a variant which predisposes towards idiopathic pancreatitis because it is carried on a TG11-M470 haplotype background, which is not a deleterious combination.3 Finally, when we screened the whole coding/flanking CFTR sequences of 10 random individuals, six polymorphisms/variants (125G/C and 875+40A/G twice, R75Q, 5T) and one cystic fibrosis mutation (ΔF508) were observed.
In conclusion, extensive analysis of CFTR sequences in a subset of patients from the south of France does not confirm a link between CFTR alterations and isolated idiopathic pancreatitis.
We thank Ms Freiss for contributing clinical data and Ms Seguret for statistical advice. This research was supported by the Direction de la Recherche Clinique, CHU, Montpellier, France (UF7533).
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.