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

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Genetic Predisposition to Disease* ; Polymorphism, Single Nucleotide*; DNA-Binding Proteins/*genetics ; Early Growth Response Protein 2/*genetics ; Oxygenases/*genetics ; Receptors, Interleukin/*genetics ; Transcription Factors/*genetics ; Uveomeningoencephalitic Syndrome/*genetics; Adult ; Alleles ; Asian People/genetics ; Carotenoids ; Case-Control Studies ; Female ; Gene Frequency ; Genome-Wide Association Study ; HLA-DR4 Antigen/genetics ; Humans ; Japan ; Male ; Middle Aged

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.

Nat Immunol. 2010 Jan;11(1):41-4. (PMID: 20016509)
Nat Genet. 2012 Nov;44(11):1222-6. (PMID: 23042114)
Hum Immunol. 1994 Mar;39(3):169-76. (PMID: 8026985)
J Ophthalmic Inflamm Infect. 2014 Jul 22;4:20. (PMID: 25097674)
Jpn J Ophthalmol. 2012 Sep;56(5):432-5. (PMID: 22752308)
Invest Ophthalmol Vis Sci. 1994 Oct;35(11):3890-6. (PMID: 7928186)
Sci Rep. 2014 Nov 10;4:6887. (PMID: 25382027)
PLoS One. 2011;6(7):e22688. (PMID: 21818367)
Jpn J Ophthalmol. 2007 Jan-Feb;51(1):41-4. (PMID: 17295139)
Science. 2006 Dec 1;314(5804):1461-3. (PMID: 17068223)
Int Ophthalmol. 2007 Apr-Jun;27(2-3):87-95. (PMID: 17253112)
Mol Vis. 2006 Dec 20;12:1601-5. (PMID: 17200659)
Nat Genet. 2009 Feb;41(2):199-204. (PMID: 19169254)
Int J Ophthalmol. 2019 Feb 18;12(2):207-211. (PMID: 30809474)
Nat Commun. 2015 Apr 09;6:6793. (PMID: 25854761)
Am J Ophthalmol. 2006 Jun;141(6):1140-1142. (PMID: 16765691)
J Clin Invest. 2006 May;116(5):1218-22. (PMID: 16670765)
Br J Ophthalmol. 2016 Mar;100(3):436-42. (PMID: 26628628)
Semin Ophthalmol. 2005 Jul-Sep;20(3):183-90. (PMID: 16282153)
Nat Genet. 2011 Jul 10;43(8):761-7. (PMID: 21743469)
Nat Genet. 2010 Aug;42(8):703-6. (PMID: 20622879)
Nat Genet. 2011 Jun 12;43(7):690-4. (PMID: 21666691)
Nat Genet. 2007 Nov;39(11):1329-37. (PMID: 17952073)
Ophthalmology. 2007 Mar;114(3):606-14. (PMID: 17123618)
Asian J Urol. 2018 Oct;5(4):205-214. (PMID: 30364478)
Am J Ophthalmol. 2001 May;131(5):647-52. (PMID: 11336942)
Nat Genet. 2008 Aug;40(8):955-62. (PMID: 18587394)
Exp Eye Res. 2005 Feb;80(2):273-80. (PMID: 15670805)
Hum Mol Genet. 2010 Jun 1;19(11):2313-20. (PMID: 20194224)
Am J Hum Genet. 2007 Feb;80(2):273-90. (PMID: 17236132)
Surv Ophthalmol. 1995 Jan-Feb;39(4):265-92. (PMID: 7725227)
J Immunol. 2000 Dec 15;165(12):7323-9. (PMID: 11120868)
Am J Ophthalmol. 2007 Aug;144(2):260-5. (PMID: 17533104)
Nat Genet. 2007 May;39(5):596-604. (PMID: 17435756)
Nat Genet. 2009 Feb;41(2):216-20. (PMID: 19122664)
Mucosal Immunol. 2009 Sep;2(5):403-11. (PMID: 19587639)
Nat Genet. 2017 Mar;49(3):438-443. (PMID: 28166214)
JAMA. 2000 Apr 19;283(15):2008-12. (PMID: 10789670)
Nature. 2015 Oct 1;526(7571):68-74. (PMID: 26432245)
JAMA. 2015 Apr 28;313(16):1657-65. (PMID: 25919529)
Nat Genet. 2014 Sep;46(9):1007-11. (PMID: 25108386)
Exp Eye Res. 2000 Oct;71(4):361-9. (PMID: 10995557)
Ocul Immunol Inflamm. 2011 Jun;19(3):202-5. (PMID: 21595536)
Retina. 1996;16(2):160-1. (PMID: 8724962)

0 (DNA-Binding Proteins)
0 (EGR2 protein, human)
0 (Early Growth Response Protein 2)
0 (HLA-DR4 Antigen)
0 (IL23R protein, human)
0 (Receptors, Interleukin)
0 (Transcription Factors)
0 (ZNF365 protein, human)
0 (beta-apocarotenoid-14',13'-dioxygenase)
36-88-4 (Carotenoids)
EC 1.13.- (Oxygenases)

Date Created: 20200522 Date Completed: 20200812 Latest Revision: 20221207

20231215

PMC7241744

10.1371/journal.pone.0233464

32437414