Investigation of the association of Vogt-Koyanagi-Harada syndrome with IL23R-C1orf141 in Han Chinese Singaporean and ADO-ZNF365-EGR2 in Thai

Br J Ophthalmol. 2016 Mar;100(3):436-42. doi: 10.1136/bjophthalmol-2015-307366. Epub 2015 Dec 1.

Abstract

Background: We performed a multistage genome-wide association study of Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population and identified two novel non-human leukocyte antigen candidate regions previously. The aim of the study was to replicate the association of IL23R-C1orf141 and ADO-ZNF365-EGR2 with VKH syndrome in four sets of multinational populations in Asia.

Method: We conducted a candidate genes association study involving 185 patients with VKH syndrome and 287 normal controls from Han Chinese Singaporeans, non-Han Chinese, Thais and Koreans. Genotyping of 16 single nucleotide polymorphisms (SNPs) within IL23R-C1orf141 and ADO-ZNF365-EGR2 loci was performed using the Sequenom MassARRAY system or by Taqman SNP assays.

Results: Eight SNPs in IL23R-Clorf141 showed an association with VKH syndrome only in Han Chinese Singaporeans (p=8.49×10(-5) to 1.02×10(-3), pcorrection=1.69×10(-4) to 2.04×10(-3)) but not in the other groups tested. One SNP rs1884444 in IL23R-Clorf141 was found to be weakly associated with VKH syndrome in the Han Chinese Singaporeans, but significance was lost following Bonferroni correction for multiple comparisons. Five SNPs in ADO-ZNF365-EGR2 were found to be associated with VKH syndrome in Thai patients with VKH (p=0.014, pc=0.028) but not in the other three ethnic groups tested.

Conclusions: This study confirmed the genetic associations between SNPs in IL23R-C1orf141 and VKH syndrome in Han Chinese Singaporeans but not in other Asian populations. In addition, we also successfully replicated the association of VKH syndrome with ADO-ZNF365-EGR2 in a Thai population.

Keywords: Genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics*
  • Carotenoids / genetics
  • Case-Control Studies
  • China / epidemiology
  • Chromosomes, Human, Pair 1 / genetics*
  • Chromosomes, Human, Pair 10 / genetics*
  • DNA-Binding Proteins / genetics
  • Early Growth Response Protein 2 / genetics
  • Eye Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotyping Techniques
  • Humans
  • Korea / epidemiology
  • Male
  • Middle Aged
  • Open Reading Frames / genetics
  • Oxygenases / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin / genetics
  • Singapore / epidemiology
  • Thailand / epidemiology
  • Transcription Factors / genetics
  • Uveomeningoencephalitic Syndrome / ethnology
  • Uveomeningoencephalitic Syndrome / genetics*

Substances

  • DNA-Binding Proteins
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • Eye Proteins
  • IL23R protein, human
  • Receptors, Interleukin
  • Transcription Factors
  • ZNF365 protein, human
  • beta-apocarotenoid-14',13'-dioxygenase
  • Carotenoids
  • Oxygenases