Pharmacogenetic Analysis of the MIR146A rs2910164 and MIR155 rs767649 Polymorphisms and Response to Anti-TNF Treatment in Patients with Crohn’s Disease and Psoriasis

Abstract

The clinical heterogeneity regarding the response profile of the antitumor necrosis factor (anti-TNF) in patients with Crohn’s disease (CD) and psoriasis (PsO) is attributed, amongst others, to genetic factors that influence the regulatory mechanisms which orchestrate the inflammatory response. Here, we investigated the possible associations between the MIR146A rs2910164 and MIR155 rs767649 variants and the response to anti-TNF therapy in a Greek cohort of 103 CD and 100 PsO patients. We genotyped 103 CD patients and 100 PsO patients via the PCR-RFLP method, utilizing the de novo formation of a restriction site for the SacI enzyme considering the MIR146A rs2910164, while Tsp45I was employed for the MIR155 rs767649 variant. Additionally, we investigated the potential functional role of the rs767649 variant, exploring in silico the alteration of transcription factor binding sites (TFBSs) mapped on its genomic location. Our single-SNP analysis displayed a significant association between the rare rs767649 A allele and response to therapy (Bonferroni-corrected p value = 0.012) in patients with PsO, a result further enhanced by the alteration in the IRF2 TFBS caused by the above allele. Our results highlight the protective role of the rare rs767649 A allele in the clinical remission of PsO, implying its utilization as a pharmacogenetic biomarker.

Pharmaco-Omics in Psoriasis: Paving the Way towards Personalized Medicine

“…In spite of its established role in the pathogenesis of the disease, the HLA-C locus presents a significant heterogeneity as a pharmacogenetic biomarker of TNFi therapy, failing to be validated in independent cohorts [ 113 , 114 , 115 , 116 , 117 ]. Additional loci that have been extensively studied in the spectrum of anti-TNF therapeutic approaches consist of the TNF-induced protein TNFAIP3 [ 114 , 118 , 119 ], the IL-12B gene [ 114 , 120 ] and NF-κB-related genes, such as MIR146A [ 121 ], NFKBIA , TNFR1B [ 114 ], TLR2 [ 122 ] and NFKBIZ [ 113 ].…”