The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, China.
University Eye Clinic Maastricht, Maastricht, The Netherlands.
J Allergy Clin Immunol. 2017 Feb;139(2):621-627. doi: 10.1016/j.jaci.2016.05.024. Epub 2016 Jun 21.
Although previous genome-wide association studies in various cohorts have identified several susceptibility loci underlying Behçet's disease (BD), this has not yet led to a breakthrough in the management of BD.
This study aimed to further investigate the association of 26 candidate single nucleotide polymorphisms with previous genome-wide association studies-identified nearly positive P values (5.0 × 10 < P < 1.0 × 10) in Chinese Han patients with BD.
A case-control association study was performed in 1206 patients with BD and 2475 healthy controls. Genotyping was performed using iPLEX Gold genotyping assay. Gene expression and cytokine production was quantified by real-time PCR and ELISA.
The results showed that significantly higher frequencies of the IL23R-IL12RB2/rs924080 TT genotype (P = 2.03 × 10; odds ratio [OR] = 1.50), IL23R-IL12RB2/rs12141431 CC genotype (P = 2.18 × 10; OR = 1.53), IL10/rs1800871 TT genotype (P = 5.88 × 10; OR = 1.47), and IL10/rs3024490 TT genotype (P = 2.80 × 10; OR = 1.34) were found in BD. Functional experiments showed an increased IL23R expression and IL-17 production in rs12141431/CC genotype carriers compared with GG genotype carriers. A decreased IL10 expression and IL-10 production was observed in rs3024490/TT genotype carriers as compared with GG genotype carriers.
Our findings not only confirmed the association of IL10/rs1800871 and IL23R-IL12RB2/rs924080 with BD but also identified 2 susceptibility single nucleotide polymorphisms in IL10 and IL23R-IL12RB2 (rs3024490 and rs12141431) with BD in Han Chinese.
尽管先前在不同队列中的全基因组关联研究已经确定了几个导致白塞病（BD）的易感基因座，但这并未导致 BD 的治疗取得突破。
本研究旨在进一步探讨 26 个候选单核苷酸多态性与先前全基因组关联研究中在汉族 BD 患者中鉴定出的接近阳性 P 值（5.0×10- < P < 1.0×10-）之间的关联。
对 1206 例 BD 患者和 2475 名健康对照进行病例对照关联研究。采用 iPLEX Gold 基因分型检测试剂盒进行基因分型。采用实时 PCR 和 ELISA 定量检测基因表达和细胞因子产生。
结果显示，IL23R-IL12RB2/rs924080 TT 基因型（P=2.03×10-；优势比[OR]=1.50）、IL23R-IL12RB2/rs12141431 CC 基因型（P=2.18×10-；OR=1.53）、IL10/rs1800871 TT 基因型（P=5.88×10-；OR=1.47）和 IL10/rs3024490 TT 基因型（P=2.80×10-；OR=1.34）在 BD 患者中的频率显著升高。功能实验显示，与 GG 基因型携带者相比，rs12141431/CC 基因型携带者的 IL23R 表达和 IL-17 产生增加。与 GG 基因型携带者相比，rs3024490/TT 基因型携带者的 IL10 表达和 IL-10 产生减少。
我们的研究结果不仅证实了 IL10/rs1800871 和 IL23R-IL12RB2/rs924080 与 BD 相关，而且还在中国汉族人群中发现了 2 个与 IL10 和 IL23R-IL12RB2（rs3024490 和 rs12141431）相关的 BD 易感单核苷酸多态性。
