PLoS ONE (Jan 2020)

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

  • Takuto Sakono,
  • Akira Meguro,
  • Masaki Takeuchi,
  • Takahiro Yamane,
  • Takeshi Teshigawara,
  • Nobuyoshi Kitaichi,
  • Yukihiro Horie,
  • Kenichi Namba,
  • Shigeaki Ohno,
  • Kumiko Nakao,
  • Taiji Sakamoto,
  • Tsutomu Sakai,
  • Tadashi Nakano,
  • Hiroshi Keino,
  • Annabelle A Okada,
  • Atsunobu Takeda,
  • Takako Ito,
  • Hisashi Mashimo,
  • Nobuyuki Ohguro,
  • Shinichirou Oono,
  • Hiroshi Enaida,
  • Satoshi Okinami,
  • Nobuyuki Horita,
  • Masao Ota,
  • Nobuhisa Mizuki

DOI
https://doi.org/10.1371/journal.pone.0233464
Journal volume & issue
Vol. 15, no. 5
p. e0233464

Abstract

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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.