Vitamin D-Related Genetics as Predictive Biomarker of Clinical Remission in Adalimumab-Treated Patients Affected by Crohn’s Disease: A Pilot Study

Abstract

Adalimumab (ADA) is a human anti-tumor necrosis factor (TNF-α) monoclonal antibody used in inflammatory bowel diseases, such as Crohn’s disease (CD). Vitamin-D (VD) is important for biological functions, such as the modulation of expression of genes encoding enzymes and transporters involved in drug metabolism and transport. ADA trough levels were associated with VD concentrations in patients with IBD, but no data are present in the literature concerning VD pathway-related gene single-nucleotide polymorphisms (SNPs) in affecting clinical outcomes. For this reason, the aim of this study was to evaluate the ability of VD-related genetics to predict clinical remission at 3 and 12 months in patients affected by CD treated with ADA. Patients affected by CD were included in this study. SNPs in CYP27B1, CYP24A1, GC, and VDR genes were analyzed through real-time PCR. A total of 63 patients were enrolled. Calprotectin, hemoglobin, and C-reactive protein levels were influenced by SNPs in VDR, CYP27B1, and GC genes. After 3 months of therapy, clinical remission was predicted by smoke, systemic steroids, and VDR BsmI, whereas at 12 months by GC 1296AA/AC and VD supplementation. This study reports the association between VD pathway-related genetics and ADA treatment. Further studies are needed to confirm these promising data.

The Role of Vitamin D in Immune System and Inflammatory Bowel Disease

“… 9 Vitamin D levels can also influence the initial response to anti-TNF-α medication in patients with IBD. 159 In addition, some vitamin D related genetic variants have already been reported associated with the remission after adalimumab treatment in CD patients, 172 which potentially supports that vitamin D might affect the efficacy of adalimumab. Moreover, as gut-tropic integrin α4β7 is another IBD immune treating target, vitamin D can downregulate gut-tropic integrin, α4β7, expression on immune cells, and higher 25(OH)D is associated with lower α4β7 positive PBMC levels and α4β7 positive intestinal leukocytes.…”

The rs11568820 Variant in the Promoter Region of Vitamin D Receptor Gene Is Associated with Clinical Remission in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

“…It is now known that polymorphisms of the VDR gene can lead to functional changes modulating the regulatory effects of vitamin D, as well as in the immune response. Indeed, associations between clinical response or remission during anti-TNFα therapy and VDR polymorphisms has been reported [15,16], but to our knowledge, this is the first study that has investigated the possible involvement of rs11568820 SNP in TNF-i treatment response.…”

“…For this reason, VDR polymorphisms with functional roles could be associated with clinical outcome and achieving remission in patients undergoing TNF-i treatment. Cusato et al described an association between VDR rs1544410 SNP and clinical remission at three months of TNF-i therapy in patients with inflammatory bowel disease (IBD) [15]. A study in patients with axial spondyloarthritis showed different improvements in C-reactive protein (CRP) and disease activity scores after 3 and 6 months of TNF-i therapy, depending on the genotype of the VDR polymorphisms rs2228570, rs731236 and rs7975232 [16].…”