# Toll-like Receptor Gene Polymorphisms as Predictive Biomarkers for Response to Infliximab in Japanese Patients with Crohn’s Disease

## TL;DR

This study finds that genetic variations in TLR1 and TLR2 genes can predict how Japanese Crohn’s disease patients respond to infliximab treatment.

## Contribution

The study identifies specific TLR gene polymorphisms as novel predictive biomarkers for infliximab response in Japanese Crohn’s disease patients.

## Key findings

- The G/G genotype of rs5743565 in TLR1 is linked to lower response rates at 10 weeks.
- C/T or T/T genotypes of rs5743604 in TLR1 and G/A or A/A genotypes of rs13105517 in TLR2 are associated with better early response.
- The A/A genotype of rs13105517 in TLR2 is linked to lower response rates after one year of treatment.

## Abstract

Objectives: To explore the possible relationship between Toll-like receptor (TLR) gene encoding and a predictive outcome for the loss of response (LOR) to IFX treatment among Japanese patients with Crohn’s disease (CD). Methods: An association analysis that involved 25 single-nucleotide polymorphisms (SNPs) across the TLR1, TLR2, TLR4, TLR6, TLR9, and TLR10 genes was performed on a cohort of 127 Japanese patients with CD. The therapeutic responses were evaluated at 10 weeks, 1 year, and 2 years using three different inheritance models. Results: The CD patients with a G/G genotype of rs5743565 in TLR1 were significantly less likely in the responders at 10 weeks compared with the non-responders (p = 0.023, OR = 0.206). The frequencies of the C/T or T/T genotypes of rs5743604 in the TLR1, G/A, or A/A genotypes of rs13105517 in TLR2, both in the minor allele dominant model, were significantly higher in the responders at 10 weeks as compared with those in the non-responders (p = 0.035, OR = 4.401; p = 0.017, OR = 5.473). The patients with an A/A genotype of rs13105517 in TLR2 in the minor allele recessive model were significantly less likely in the responders at one year of IFX treatment compared with those in the non-responders (p = 0.004, OR = 0.195). Conclusions: The polymorphisms of TLR1 and TLR2 can be useful as biomarkers for predicting initial and secondary LOR to IFX in Japanese CD patients. The IFX response in genetic testing may target molecules for new drugs to overcome the non-response and LOR to IFX.