Polymorphisms in NFKBIA and ICAM-1 genes in New Zealand Caucasian Crohn's disease patients

Abstract

Crohn's disease (CD) is a complex polygenetic inflammatory disease of the bowel. NFKBIA (IkappaBalpha) is a downstream regulator of NF-kappaB, which is an effector of the major Crohn's susceptibility gene CARD15/NOD2. ICAM-1 is an integrin ligand and vascular addressin, which contributes to the trafficking of pathogenic leukocytes into the inflamed bowel. Here we examined whether the NFKBIA 2758G/A and ICAM-1 K469E variants, recently shown to be CD susceptibility genes in Caucasian populations in Germany and the United Kingdom, are associated with CD in Caucasian patients in New Zealand. PCR-RFLP analysis was used to examine the frequency of gene polymorphisms in 182 CD patients and 188 ethnically matched controls. There was no significant evidence of a difference in the allele frequency of either the 2758G/A polymorphism in NFKBIA (0.38 vs 0.35, P = 0.47) or the K469E polymorphism in ICAM-1 (0.43 vs 0.37, P = 0.10) between CD patients and controls. Nevertheless, the ICAM-1 469E allele significantly (P = 0.016, Pc = 0.047) influenced the age of diagnosis of CD. Meta-analysis with five other studies confirmed a lack of association of the K469E polymorphism with Crohn's disease (P = 0.33; OR = 0.93; 95% CI, 0.82-1.07). The NFKBIA 2758G/A and ICAM-1 K469E polymorphisms are not significant risk factors for CD in New Zealand; however, there is evidence that the latter polymorphism influences the age of diagnosis.