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Hum Genet. 2013 Sep;132(9):1049-58. doi: 10.1007/s00439-013-1312-5. Epub 2013 May 15.

Genetic variants in the JAK1 gene confer higher risk of Behcet's disease with ocular involvement in Han Chinese.

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The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400016, People's Republic of China.


Recent surveys have identified SLC22A4, SLC22A5, RUNX1, JAK1 as susceptibility genes for various immune-related diseases. An association study was performed in 738 Behcet's patients with ocular involvement and 1,873 controls using the iPLEX system method. The first-stage study for 30 SNPs showed that SNPs rs2780815, rs310241, rs3790532 in JAK1 were associated with Behcet's disease in Han Chinese (Pc(Bonferroni correction) = 0.022-7.7 × 10(-3)). The G allele and AA genotype of SNP rs2834643 in RUNX1 (Pc = 0.041-1.75 × 10(-3)), but none of the other SNPs, were associated with Behcet's disease. Haplotype analysis for the SLC22A4, SLC22A5 genes showed an increased tendency for AGTCTGCCGC frequency in patients compared with controls; however, the significance was lost after Bonferroni correction (P = 0.004, Pc > 0.05). Subsequently, we further replicated the significantly associated SNPs using another independent cohort. Replication and combining studies showed that three SNPs rs2780815, rs310241, rs3790532 in JAK1, but not SNP rs2834643 in RUNX1, were consistently associated with Behcet's disease (replication: Pc = 0.012-9.60 × 10(-4); combining: Pc = 0.030-1.90 × 10(-4)). SNPs rs2780815, rs310241, rs3790532 were estimated to confer a population attributable risk of 35.0, 28.0, 27.0 %, respectively. We found a strong association between HLA-B51 with Behcet's disease in Chinese Han population (P = 1.35 × 10(-73); OR = 5.15; 95 % CI 4.28-6.19). GMDR analysis showed that no gene-gene interaction was detectable between JAK1 and HLA-B51. Logistic analysis indicated that the JAK1 gene was an independent risk factor for Behcet's disease (P > 0.05). Real-time PCR analysis showed that no difference on the expression of JAK1 in PBMCs or LPS-stimulated PBMCs between individuals with the different rs1762780815 genotypes studied (P > 0.05). In conclusion, this study suggests that JAK1, but not SLC22A4, SLC22A5 and RUNX1, contributes to the genetic susceptibility to Behcet's disease with ocular involvement.

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