AB0008 Lack of Association between Polymorphisms in Interlukin (IL-12, IL-12R, IL-23, IL-23R Genes and Takayasu Arteritis in A Chinese Population
Authors: K.-Q. Yang, Y.-K. Yang, D. Wen, X. Meng, Y. Zhang, X.-J. Jiang, H.-Y. Wu, H.-M. Zhang, L. Song, J. Bian, X.-L. Zhou
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Takayasu arteritis (TA) is a chronic inflammatory arteritis with unknown cause. Genetic components may play an important role in the pathogenesis of TA. It is indicated that HLA-B*52 allele contributes to TA development worldwide. <i>IL12B</i> is identified as a susceptibility gene for TA in two recent genome-wide association studies. To date, several loci in the genes coding for members of the IL-12/IL-23 pathway have been found to be involved in the pathogenesis of various immune-mediated diseases. <h3>Objectives</h3> The goal of this study was to investigate the relationship between polymorphisms in interleukin (IL)-12, IL-12R, IL-23, and IL-23R genes and TA in a Chinese population. <h3>Methods</h3> A case-control study was performed to investigate the associations of nineteen single nucleotide polymorphisms (SNPs) mapping to <i>IL12A</i>, <i>IL12B</i>, <i>IL12RB1</i>, <i>IL12RB2</i> and <i>IL23R</i> with susceptibility to TA in 145 Chinese TA patients and 300 healthy controls. Genotype identification was performed with the MassARRAY system from Sequenom. In addition, HLA-B*52 genotypes were detected by the polymerase chain reaction using the sequence-specific primers (PCR-SSP).The statistical analysis was conducted by chi-square test and unconditional Logistic regression with plink. <h3>Results</h3> No significant differences were found for the distribution of allele and genotype frequencies of these SNPs between TA patients and healthy controls. However, a trend for <i>IL12A</i> rs582054 and <i>IL23R</i> rs1004819 in association with the TA phenotype was detected. TA patients carrying the rs582054/ rs568408 haplotype (<i>P</i><sub>c</sub>=0.019) appeared less likely to progress to a more severe form of disease. And the C allele (<i>P</i><sub>c</sub>=0.082) of <i>IL23R</i> rs1004819 appeared to be a protective factor to refractory disease. The association of TA with HLA-B*52 was confirmed in this cohort of Chinese patients. Whereas, there was no interaction between HLA-B*52 and polymorphisms in IL-12/IL-23 axis genes. <h3>Conclusions</h3> These findings suggest that the polymorphisms of <i>IL12A</i>, <i>IL12B</i>, <i>IL12RB1</i>, <i>IL12RB2</i> and <i>IL23R</i> might make no contribution to the susceptibility of TA in the Chinese population. <h3>References</h3> Terao C. Revisited HLA and non-HLA genetics of Takayasu arteritis-where are we? J Hum Genet. 2015. doi: 10.1038/jhg.2015.87. Terao C, Yoshifuji H, Kimura A et al. Two susceptibility loci to Takayasu arteritis reveal a synergistic role of the IL12B and HLA-B regions in a Japanese population. Am J Hum Genet. 2013; 93:289–97. Saruhan-Direskeneli G, Hughes T, Aksu K et al. Identification of multiple genetic susceptibility loci in Takayasu arteritis. Am J Hum Genet. 2013; 93:298–305. van Wanrooij RL, Zwiers A, Kraal G, Bouma G. Genetic variations in interleukin-12 related genes in immune-mediated diseases. J Autoimmun. 2012; 39:359–68. Duvallet E, Semerano L, Assier E, Falgarone G, Boissier MC. Interleukin-23: a key cytokine in inflammatory diseases. Ann Med. 2011;43:503–11. <h3>Disclosure of Interest</h3> None declared