PSC and CFTR

[Guest guest]

The link between PSC and the cystic fibrosis transmembrane

conductance regulator gene (CFTR) just doesn't seem to want to go

away ....

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J. Hepatol. [in Press] (2008)

Cystic fibrosis transmembrane conductance regulator gene

polymorphisms in patients with primary sclerosing cholangitis.

Liesbet Henckaerts1, e Jaspers2, Werner Van Steenbergen3,

Liesbet Vliegen2, Johan Fevery3, Hilde Nuytten2, Tania Roskams4,

Rutgeerts1, Jean-Jacques Cassiman2, Séverine Vermeire1, Harry Cuppens2

Received 14 May 2008; received in revised form 16 July 2008; accepted

21 July 2008. published online 02 October 2008.

Uncorrected Proof

Background/Aims

Primary sclerosing cholangitis (PSC) is a progressive cholestatic

disease commonly associated with inflammatory bowel disease (IBD) and

characterized by fibrosing inflammatory destruction of bile ducts.

The histological features in the liver of PSC patients are similar to

those observed in cystic fibrosis (CF). Our aim was to study whether

variants in the CFTR gene are associated with the occurrence and/or

evolution of PSC.

Methods

PSC patients (n=140) were genotyped for F508del, the TGmTn variants,

and four additional polymorphic loci (1001+11 C>T, M470V, T854T and

Q1463Q), and compared to 136 matched healthy controls.

Results

The 1540G-allele, encoding V470, was less frequent in PSC (52%) than

in controls (64%, p=0.003), and was associated with protection

against PSC in individuals without IBD (OR 0.25, 95% CI 0.12-0.52,

p=0.0002). Also TG11-T7 was less frequent in PSC (53%) than in

controls (61%, p=0.04). This haplotype was associated with reduced

risk for PSC (OR 0.34, 95% CI 0.17-0.70, p=0.003) in individuals

without IBD.

Conclusion

In this cohort of PSC patients, several CFTR-variants affecting the

functional properties of the CFTR protein seem to offer protection

against the development of PSC, confirming our hypothesis that CFTR

might be implicated in the pathogenesis of PSC.

Abbreviations: CCA, cholangiocarcinoma, CD, Crohn's disease, CF,

cystic fibrosis, CFTR, cystic fibrosis transmembrane conductance

regulator, DNA, desoxyribonucleic acid, FDR, false discovery rate,

IBD, inflammatory bowel disease, IC, indeterminate colitis, LD,

linkage disequilibrium, OR, odds ratio, PCR, polymerase chain

reaction, PSC, primary sclerosing cholangitis, UC, ulcerative colitis

Keywords: Biliary tract diseases, Disease susceptibility, Genetics,

Membrane proteins, Pattern recognition receptors

1 Department of Gastroenterology, University Hospital Gasthuisberg,

Catholic University of Leuven, Herestraat 49, B-3000 Leuven, Belgium

2 Department of Human Genetics, Division of Human Mutations and

Polymorphisms, Catholic University of Leuven, Leuven, Belgium

3 Department of Liver, Biliary and Pancreatic Diseases, University

Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium

4 Department of Pathology, University Hospital Gasthuisberg, Catholic

University of Leuven, Leuven, Belgium

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While the link between PSC and CFTR is not particularly new, perhaps

what's more significant about this article is that it's from

respected IBD genetic researchers ( Rutgeerts and Séverine

Vermeire), suggesting that they may be turning their attention to

PSC, which would be good news for us.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)