Variants in IL23R-C1orf141 and ADO-ZNF365-EGR2 are associated with susceptibility to Vogt-Koyanagi-Harada disease in Japanese population.

Autor: Sakono T; Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanagawa, Japan., Meguro A; Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanagawa, Japan., Takeuchi M; Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanagawa, Japan., Yamane T; Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanagawa, Japan., Teshigawara T; Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.; Yokosuka Chuoh Eye Clinic, Kanagawa, Japan.; Tsurumi Chuoh Eye Clinic, Kanagawa, Japan., Kitaichi N; Department of Ophthalmology, Health Sciences University of Hokkaido, Hokkaido, Japan., Horie Y; Department of Ophthalmology, Health Sciences University of Hokkaido, Hokkaido, Japan., Namba K; Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan., Ohno S; Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan., Nakao K; Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Sakamoto T; Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Sakai T; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan., Nakano T; Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan., Keino H; Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan., Okada AA; Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan., Takeda A; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Ito T; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Mashimo H; Department of Ophthalmology, Japan Community Health care Organization Osaka Hospital, Osaka, Japan., Ohguro N; Department of Ophthalmology, Japan Community Health care Organization Osaka Hospital, Osaka, Japan., Oono S; Department of Ophthalmology, Saga University Faculty of Medicine, Saga, Japan.; Hoshiai Eye Clinic, Saitama, Japan., Enaida H; Department of Ophthalmology, Saga University Faculty of Medicine, Saga, Japan., Okinami S; Department of Ophthalmology, Saga University Faculty of Medicine, Saga, Japan.; Department of Ophthalmology, Kurashiki Central Hospital, Okayama, Japan., Horita N; Department of Pulmonology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan., Ota M; Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.; Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Nagano, Japan., Mizuki N; Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 May 21; Vol. 15 (5), pp. e0233464. Date of Electronic Publication: 2020 May 21 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0233464
Abstrakt: Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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