NCF1 (p47phox) and NCF1 Pseudogenes Are Not Associated with Inflammatory Bowel Disease

Abstract

Crohn's disease (CD) and ulcerative colitis (UC) have a strong genetic component, contributing to a patient's susceptibility for inflammatory bowl disease (IBD). Linkage analysis has detected an IBD susceptibility locus in a region on chromosome 7q that encompasses the p47 (NCF1) gene and p47 (PsiNCF1) pseudogenes. Involvement of the NCF1 locus in IBD was supported by the observation that chronic inflammation of the bowel is a feature of chronic granulomatous disease caused by NCF1 mutation in 25% of cases. The pseudogenes have a dinucleotide deletion (PsiGT) at the beginning of exon 2, resulting in a frameshift and premature stop codon. APsiNCF1 (DeltaGT) to NCF1 (GTGT) ratio of 2:1 has been proposed as the predominant ratio in humans; but variability may occur after DNA exchange by recombination between PsiNCF1 and NCF1 to produce a potentially functional gene hybrid (type IIPsiNCF1). A preliminary study suggested an association between individuals with a 1:1 ratio and susceptibility to IBD. The possible presence of type IIPsiNCF1 was proposed as a susceptibility factor. We have now established the PsiNCF1 to NCF1 ratio for a significant number of IBD patients (n = 488) and control subjects (n = 181) and show that there is no statistically significant difference between the frequency of the 1:1 ratio in CD (11.2%) or UC (12.2%) patients and controls (13.4%). The 2:1 ratio was identified as the most common ratio (83.3%). Our data show there is no association of the 1:1 ratio with IBD and that susceptibility is unlikely to be a consequence of an inherited 1:1, rather than a 2:1 (PsiNCF1:NCF1) ratio.