TY - JOUR
T1 - HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients
AU - NCBN Controls WGS Consortium
AU - Shimoda, Fumiko
AU - Naito, Takeo
AU - Kakuta, Yoichi
AU - Kawai, Yosuke
AU - Tokunaga, Katsushi
AU - Ishibashi-Ueda, Hatsue
AU - Tomita, Tsutomu
AU - Noguchi, Michio
AU - Takahashi, Ayako
AU - Goto, Yu ichi
AU - Yoshida, Sumiko
AU - Hattori, Kotaro
AU - Matsumura, Ryo
AU - Iida, Aritoshi
AU - Maruoka, Yutaka
AU - Gatanaga, Hiroyuki
AU - Sugiyama, Masaya
AU - Suzuki, Satoshi
AU - Miyo, Kengo
AU - Matsubara, Yoichi
AU - Umezawa, Akihiro
AU - Hata, Kenichiro
AU - Kaname, Tadashi
AU - Ozaki, Kouichi
AU - Tokuda, Haruhiko
AU - Watanabe, Hiroshi
AU - Niida, Shumpei
AU - Noiri, Eisei
AU - Kitajima, Koji
AU - Omae, Yosuke
AU - Miyahara, Reiko
AU - Shimanuki, Hideyuki
AU - Shimoyama, Yusuke
AU - Moroi, Rintaro
AU - Shiga, Hisashi
AU - Nagasaki, Masao
AU - Kinouchi, Yoshitaka
AU - Masamune, Atsushi
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/11
Y1 - 2023/11
N2 - 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 biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E−9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E−5 and 5.80E−4, respectively).
AB - 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 biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E−9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E−5 and 5.80E−4, respectively).
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U2 - 10.1038/s41397-023-00312-z
DO - 10.1038/s41397-023-00312-z
M3 - Article
C2 - 37460671
AN - SCOPUS:85165037554
SN - 1470-269X
VL - 23
SP - 141
EP - 148
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
IS - 6
ER -