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Takuto Sakono, Akira Meguro, Shigeaki Ohno, Taiji Sakamoto, Hiroshi Tsuneoka, Annabelle A Okada, Takako Fukuhara, Nobuyuki Ohguro, Satoshi Okinami, Nobuhisa Mizuki; Replication of previous genome-wide association study findings for Vogt-Koyanagi-Harada disease in a Japanese population.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6565.
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© ARVO (1962-2015); The Authors (2016-present)
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 anterior uveitis). Although the exact etiology and pathogenic mechanism of VKH disease remain unclear, HLA-DR4 alleles have been proved to be strongly associated with VKH in various ethnic groups. However, some patients have VKH disease without carrying HLA-DR4 risk alleles, implying that other genetic and/or environmental factors may also act as risk factors for pathogenesis. Recently, a genome-wide association study (GWAS) of VKH disease in a Han Chinese population reported two susceptibility loci at 1p31.2 and 10q21.3 (Nat Genet 2014;46(9):1007-11.). In this study, we sought to replicate the GWAS findings in a Japanese population.
One thousand six hundred and forty-three Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four SNPs reportedly associated with VKH disease in the previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141 at 1p31.2, and rs442309 and rs224058 in ADO-ZNF365-EGR2 at 10q21.3.
Significant association with VKH disease was observed at the IL23R-C1orf141 locus (rs78377598: p=0.0014; rs117633859: p=0.00043). The T allele of rs78377598 and the G allele of rs117633859 were associated with an increased risk of VKH disease (OR=1.65 and OR=1.71, respectively). The ADO-ZNF365-EGR2 locus also showed significant association with the disease (rs442309: p=0.0053; rs224058: p=0.0088). The T allele of rs442309 and the A allele of rs224058 were associated with an increased risk of VKH disease (OR=1.27 and OR=1.25, respectively).
Our results replicate associations reported recently in the previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play an important role in the development of VKH disease through genetic polymorphisms.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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