The +1059G/C polymorphism in the C-reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum CRP levels in patients with Crohn's disease

Abstract

Background: Serum C-reactive protein (CRP) levels influence the response to anti-tumour necrosis factor (TNF) therapies.

Aim: To analyse the influence of the +1059G/C CRP polymorphism on CRP serum levels and disease susceptibility in patients with Crohn's disease (CD).

Methods: Using restriction fragment length polymorphism (RFLP) analysis, genomic DNA from 241 CD patients and 199 unrelated controls was analysed for the +1059G/C substitution in the CRP gene and the common caspase-activation recruitment domain 15 (CARD15) variants.

Results: Homozygous C/C carriers were detected only among CD patients (P = 0.066). Patients with ileal involvement (L1 and L3 phenotype) were found in only 58.4% of patients with the wildtype G/G genotype but in 88.2% of the heterozygous G/C carriers (OR 5.26; 95% CI 1.19-23.92) and four of the five C/C homozygous carriers (80%; OR 4.55; 95% CI 1.64-16.67; P = 0.008 for hetero- and homozygous carriers vs. wildtype) which was independent of the presence of CARD15 variants. Increased CD activity was associated with increased CRP serum levels (P < 0.005). For Crohn's disease activity index (CDAI) < 150, C/C homozygosity for the +1059 G/C polymorphism was associated with significantly lower CRP serum levels (P < 0.01).

Conclusions: The C allele of the CRP +1059G/C polymorphism is associated with decreased serum CRP levels and increased likelihood of disease involvement of the terminal ileum in CD patients.