NOD2/CARD15 SNP8, 12 and 13 and other EXON4 mutations and primary biliary cirrhosis (PBC) in Hungarian and Polish patients

P. L. Lakatos; C. Willheim-Polli; A. Folhoffer; A. Horvath; T. Csák; C. Österreicher; A. Habior; I. Tornai; P. Ferenci; F. Szalay

doi:10.1055/s-2004-826980

Zeitschrift für Gastroenterologie, Inhaltsverzeichnis

NOD2/CARD15 SNP8, 12 and 13 and other EXON4 mutations and primary biliary cirrhosis (PBC) in Hungarian and Polish patients

PL Lakatos ¹, C Willheim-Polli ², A Folhoffer ¹, A Horvath ¹, T Csák ¹, C Österreicher ², A Habior ³, I Tornai ⁴, P Ferenci ², F Szalay ¹

¹1st Dept. of Med, Semmelweis University, Budapest
²Dept. of Intern. Med. 4, University of Vienna, Austria
³Dept. of Gastroenterol, Medical Center for Postgrad Educ, Warsaw, Poland
⁴2nd Dept. of Intern Med, Debrecen University, Debrecen

Abstract

Mutations of the NOD2/CARD15 gene –coding a bacterial LPS receptor- were identified as genetic markers for Crohn's disease (CD). PBC shares some features of CD (e.g. possible infectious etiology, granulomas). It has been suggested that infection by bacteria and cross-reactivity between bacterial and self-proteins may be an important factor in the pathogenesis. In this study the presence of common NOD2/CARD15 mutations were investigated in Hungarian and Polish PBC patients.

Patients and methods: 88 patients with PBC (each female, mean age: 61.4 (SD 9.6) years) were included in this study. A set of 200 healthy blood donors served as control. DNA was screened for possible mutations by denaturing HPLC (WAVE Nucleic acid fragment analysis systems, Cheshire, UK) using published primers. Mutations were than confirmed by direct sequencing on a ABI Prism 310 Genetic Analyzer (Perkin Elmer; Norwalk, USA).

Results: Mutations of NOD2/CARD15 were found in 13 (14.8%) PBC patients (4 heterozygous and 1 homozygous for R702W [SNP8], one heterozygous for a further exon4 mutation (R791Q), 3 heterozygous for G908W [SNP12] and 4 heterozygous for 3020insC [SNP13]) and in 33 controls (16.5%, all heterozygous). There was no difference in the allele frequency of R702W (3.4 vs. 3.1%), G908W (1.7 vs. 1.8%) or 3020insC (2.3% vs. 2.5%) between PBC patients and controls.

Conclusions: The presence of NOD2/CARD15 mutations was not different between PBC patients and controls such it is unlikely that (at least SNP8, 12 and 13) NOD2 mutations play an important role in the pathogenesis of PBC.