Transferrin Level Before Treatment and Genetic Polymorphism in HFE Gene as Predictive Markers for Response to Adalimumab in Crohn's Disease Patients

Biochem Genet. 2016 Aug;54(4):476-486. doi: 10.1007/s10528-016-9734-0. Epub 2016 Apr 26.

Abstract

Tumor necrosis factor α inhibitors (anti-TNF) have improved treatment of several complex diseases, including Crohn's disease (CD). However, the effect varies and approximately one-third of the patients do not respond. Since blood parameters as well as genetic factors have shown a great potential to predict response during treatment, the aim of the study was to evaluate response to anti-TNF treatment with adalimumab (ADA) between genes HFE and TF and haematological parameters in Slovenian refractory CD patients. Single nucleotide polymorphisms (SNPs) rs1799852 in gene TF and rs2071303 in gene HFE were genotyped in 68 refractory CD patients for which response has been measured using inflammatory bowel disease questionnaire (IBDQ) index. Haematological parameters and IBDQ index were determined before therapy and after 4, 12, 20 and 30 weeks. We found novel strong association between SNP rs2071303 in gene HFE and response to ADA treatment, particularly patients with G allele comparing to A allele had better response after 20 weeks (p = 0.008). Further, we found strong association between transferrin level at baseline and treatment response after 12, 20 and 30 weeks, where average transferrin level before therapy was lower in responders (2.38 g/L) compared to non-responders (2.89 g/L, p = 0.005). Association was found between transferrin level in week 30 and SNP rs1799852 (p = 0.023), and between MCHC level before treatment and SNP rs2071303 (p = 0.007). Our results suggest that SNP in gene HFE as well as haematological markers serve as promising prognostic markers of response to anti-TNF treatment in CD patients.

Keywords: Adalimumab; Anti-TNF; HFE gene; TF gene; Transferrin.

MeSH terms

  • Adalimumab / therapeutic use*
  • Crohn Disease / drug therapy*
  • Crohn Disease / genetics
  • Crohn Disease / metabolism
  • Gene Expression Regulation / drug effects
  • Genetic Markers
  • Genotype
  • Hemochromatosis Protein / genetics*
  • Humans
  • Polymorphism, Single Nucleotide*
  • Slovenia
  • Transferrin / genetics*
  • Transferrin / metabolism
  • Treatment Outcome

Substances

  • Genetic Markers
  • HFE protein, human
  • Hemochromatosis Protein
  • Transferrin
  • Adalimumab