HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients

Abstract

Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early Infliximab (IFX) treatment failure in the Caucasian Crohn’s disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese IFX-naiveCD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The rs2097432 significantly increased the risk of early discontinuation of IFX even after being adjusted by other clinical parameters [Hazard ratio (HR) = 2.13 and P-value = 0.038]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B, reached genome-wide significance (HR = 6.04 and P-value = 7.93E-9). We confirmed the robust association of rs2097432 with IFX persistence regardless of the population. A novel genetic factor for IFX persistence was also identified using GWAS.