JAK1, but NotJAK2andSTAT3, Confers Susceptibility to Vogt–Koyanagi–Harada (VKH) Syndrome in a Han Chinese Population

Abstract

PURPOSE. Janus kinase 1 (JAK1), JAK2, and signal transducer and activator of transcription 3 (STAT3) play an important role in Th1 and Th17 differentiation and gene polymorphisms of these factors have been demonstrated to be associated with certain autoimmune diseases. The present study was performed to assess the association between JAK1, JAK2, and STAT3 polymorphisms and Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population. METHODS.A case-control study was performed in 737 Chinese VKH syndrome patients and 809 healthy controls from a Han Chinese population. The genotypes of three singlenucleotide polymorphisms (SNPs) (rs310230, rs310236, rs310241) in JAK1 were performed using an SNP genotyping system. Three SNPs (rs10758669, rs7857730, rs10119004) in JAK2 and four SNPs (rs6503695, rs744166, rs2293152, and rs12948909) in STAT3 were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Hardy-Weinberg equilibrium (HWE) was tested using the v 2 test. Genotype frequencies were estimated through direct counting. Allele and genotype frequencies were compared between patients and controls using the v 2 test.RESULTS. There was no deviation from the HWE in all controls tested. Three SNPs, including rs310230, rs310236, and rs310241, in JAK1 were significantly associated with VKH syndrome (Pc ¼ 0.008, 0.005, 0.001, respectively). None of the tested SNPs of JAK2 and STAT3 was associated with VKH syndrome. Stratification analysis according to headache, dysacusis, alopecia, poliosis, and vitiligo for VKH syndrome did not reveal an association.CONCLUSIONS. These results suggest that JAK1 genetic polymorphisms, but not JAK2 and STAT3, are associated with the susceptibility to VKH syndrome.

Lack of Association between Genetic Polymorphisms of JAK-STAT Signaling Pathway Genes and Acute Anterior Uveitis in Han Chinese

“…Four SNPs (rs6718902, rs10199181, rs2066802, and rs1547550) in the STAT1 gene were observed to be associated with MS in Italy and IgA nephropathy (IgAN) in Korea [39, 40]. In addition, an association was found between SNPs (rs2780815, rs310241, rs3790532, rs310230, and rs310236) in JAK1 and Behçet disease (BD) as well as Vogt-Koyanagi-Harada (VKH) syndrome [41, 42], two other common uveitis entities in China. There has been no report of associations between JAK-STAT signaling pathway genes and AAU, and thus we performed this case-control study to detect whether the five candidate genes were associated with AAU in a Chinese Han population.…”

“…We used HaploView 4.2 software to evaluate the linkage disequilibrium (LD) and minor allele frequency (MAF) of the SNPs. Five SNPs of JAK1 , rs2780815, rs3790532, rs310230, rs310236, and rs310241 [41, 42], were selected. Since the SNPs rs3790532, rs310230, rs310236, and rs310241 are in strong LD with each other ( r 2 > 0.8, Figure 1), we only used rs310241 in our study.…”

Pigmentary disorders of the eyes and skin

“…VKH likely results from the complex interplay of genetic and environmental factors. [120][121][122][123][124][125][126][127][128] There are several criteria required for diagnosis. 129 …”

Influence of molecular genetics in Vogt-Koyanagi-Harada disease

“…A recent study suggested that three SNPs of the JAK1 gene including GG genotype of rs310230, GG genotype of rs310236, and TT genotype of rs310241 were found to occur in lower frequencies in VKH patients than control subjects [[150]]. However, no significant link between the three SNPs and clinical manifestations of VKH disease was identified, and currently, there is no published data on the functional role of these SNPs of JAK1 [[150]].…”