No association between C-reactive protein gene polymorphisms and decrease of C-reactive protein serum concentration after infliximab treatment in Crohn's disease

Abstract

We recently showed an association between the FCGR3A V/F polymorphism and the biological response [assessed on the basis of a C-reactive protein (CRP) concentration decrease] to infliximab in Crohn's disease. The CRP and FCGR3A genes are located on the same 1q23 locus. The present study aimed: (i) to exclude a linkage disequilibrium (LD) between the two genes and (ii) to study the association between CRP polymorphisms and the response to infliximab, particularly the decrease in CRP after treatment, in Crohn's disease patients. FCGR3A (V/F) polymorphism and three CRP polymorphisms (-717G/A, 1444C/T, CRP 4A/G) were determined in 206 healthy blood donors and 189 Crohn's disease patients who had received infliximab for either refractory luminal or fistulizing Crohn's disease. Clinical response was defined as complete, partial or absent according to the same definition as in controlled trials. The biological response was defined on the basis of CRP decrease. There was no LD between CRP and FCGR3A in healthy donors or Crohn's disease patients. CRP polymorphisms had no impact on CRP decrease after infliximab. The proportions of Crohn's disease having a positive clinical or biological response were not statistically different among the various genotypes of CRP polymorphisms. There was no LD between CRP and FCGR3A polymorphisms. CRP polymorphisms were not associated with the response to infliximab in Crohn's disease.

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

“…20 These observations are in apparent contrast to results obtained in coronary heart disease or in SLE, where the CRP 1444T allele and the CRP 4A allele were associated with higher and lower CRP concentrations, respectively. 13,14 However, in a recent study of a cohort of patients with coronary heart disease and a population of controls, this association could not be confirmed.…”

“…Because of the small sample size, the influence of the +1059G/C polymorphism on the response to infliximab could not been determined in this study. One of the main reasons for the discrepancies regarding the effect of certain CRP polymorphisms on CRP serum levels in different studies 13,14,20 may be that those CRP variants lead to slight variations in low CRP levels in healthy individuals or diseases which do not result in a significant elevation of CRP. 50 Furthermore, an association with higher levels of CRP in diseases such as CD, which is associated with a pronounced elevation of this protein, is difficult to analyse, because the heterogeneity in the degree of inflammatory reaction is a major confounding factor.…”

“…This polymorphism is so far the most extensively studied CRP SNP and has been shown to affect CRP serum levels in healthy male blood donors. 15 However, in contrast to other CRP polymorphisms, 20 its role in CD has not been analysed yet.…”

“…It has been hypothesized that the paradoxical absence of a CRP increase in some patients with clinically active CD may be because of a genetic predisposition to produce less CRP. 20 Indeed, family studies have suggested that 30-40% of the variation in plasma CRP concentration is genetically determined. 7 CRP elevation in inflammatory bowel disease (IBD) patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation.…”

“…We focused on the CRP (G fi C) +1059 SNP in exon 2, which is so far the most extensively characterized CRP SNP and has been shown to decrease CRP serum levels 15 while in contrast no association for three other CRP polymorphisms ()717G/A, 1444C/T, CRP 4A/G) with CD and CRP levels after infliximab treatment could be demonstrated in CD patients. 20 Moreover, a recent study demonstrated that patients with CD and a persistently low CRP despite active disease were characterized by an almost exclusive ileal disease distribution. 21 Given the previously described CRP lowering effect of the +1059G/C CRP polymorphism, 15 we therefore hypothesized that this polymorphism may be a risk factor for ileal disease location.…”