Year: 2020
Type: review
Study design: Observational Study
Abstract: Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside theHLAcomplex,CCL24,STYXL1-SRRM3, andC1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10−8) with sarcoidosis;CCL24andSTYXL1-SRRM3were novel. The disease-risk alleles inCCL24andIL23Rwere associated with reducedCCL24andIL23Rexpression, respectively. The disease-risk allele inSTYXL1-SRRM3was associated with elevatedPORexpression. These results suggest that genetic control ofCCL24,POR, andIL23Rexpression contribute to the pathogenesis of sarcoidosis. We speculate that theCCL24risk allele might be involved in a polarized Th1 response in sarcoidosis, and thatPORandIL23Rrisk alleles may lead to diminished host defense against sarcoidosis pathogens.
Source: Communications Biology
Authors: Akira Meguro, Mami Ishihara, Martin Petrek, Ken Yamamoto, Masaki Takeuchi, Frantisek Mrazek, Vitezslav Kolek, Alzbeta Benicka, Takahiro Yamane, Etsuko Shibuya, Atsushi Yoshino, Akiko Isomoto, Masao Ota, Keisuke Yatsu, Noriharu Shijubo, Sonoko Nagai, Etsuro Yamaguchi, Tetsuo Yamaguchi, Kenichi Namba, Toshikatsu Kaburaki, Hiroshi Takase, Shin-ichiro Morimoto, Junko Hori, Keiko Kono, Hiroshi Goto, Takafumi Suda, Soichiro Ikushima, Yasutaka Ando, Shinobu Takenaka, Masaru Takeuchi, Takenosuke Yuasa, Katsunori Sugisaki, Nobuyuki Ohguro, Miki Hiraoka, Nobuyoshi Kitaichi, Yukihiko Sugiyama, Nobuyuki Horita, Yuri Asukata, Tatsukata Kawagoe, Ikuko Kimura, Mizuho Ishido, Hidetoshi Inoko, Manabu Mochizuki, Shigeaki Ohno, Seiamak Bahram, Elaine F. Remmers, Daniel L. Kastner, Nobuhisa Mizuki
Institutions: Yokohama City University, Palacký University Olomouc, Kurume University, Kyushu University, Medical Institute of Bioregulation, Kyushu University, National Institutes of Health, National Human Genome Research Institute, National Defense Medical College, Shinshu University, Inserm, Aichi Medical University, Aichi Medical University Hospital, JR Tokyo General Hospital, Tokyo General Hospital, Hokkaido University, The University of Tokyo, Tokyo Medical and Dental University, Fujita Health University, Nippon Medical School, Tokyo Medical University, Hamamatsu University, Hamamatsu University School of Medicine, Japanese Red Cross Medical Center, Keio University, Kitasato Institute Hospital, Kumamoto City Hospital, National Hospital Organization, Nishibeppu National Hospital, Osaka Hospital, Japan Community Healthcare Organization, Sapporo Medical University, Health Sciences University of Hokkaido, Jichi Medical University, Tokai University, Université de Strasbourg
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,290
Awards: Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app, Imputation-based genome-wide association study of sarcoidosis, Analysis of epidermal growth factor receptor dependent inflammation amplifier activation in uveitis, Identification of genes associated with the development of organ lesions in sarcoidosis, Genetic analysis of sarcoidosis in a multi-ethnic cohort
OpenAlex ID: W3081189322