Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, People's Republic of China.
The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, People's Republic of China.
Pediatr Res. 2020 Mar;87(4):634-638. doi: 10.1038/s41390-019-0612-4. Epub 2019 Oct 16.
Previous studies have shown that aberrant T lymphocyte apoptosis is involved in the pathogenesis of uveitis. Genetic variants of apoptotic pathway-related factors (including PDCD1, PDCD1LG2, FAS, and FASLG) may affect apoptosis and in turn predict susceptibility to autoimmune disease. This has not yet been studied in pediatric idiopathic uveitis (PIU) and juvenile idiopathic arthritis (JIA)-associated uveitis and was therefore the subject of the study presented here.
Fourteen single-nucleotide polymorphisms (SNPs) of several apoptosis-related pathway genes were analyzed in 1238 PIU patients, 128 JIA-associated uveitis patients and 1114 healthy controls using the iPLEX Gold Assay and MassARRAY platform.
A lower frequency of the PDCD1/rs6710479 CC genotype in PIU patients was found when compared to controls (Pc = 3.42 × 10). A higher frequency of the PDCD1/rs7421861 A allele (Pc = 4.85 × 10) was observed in PIU patients as compared with controls. Stratification analysis showed a positive association of band keratopathy with the PDCD1/rs7565639 CT genotype (Pc = 1.05 × 10) and a negative association of this parameter with the PDCD1/rs7565639 C allele (Pc = 3.76 × 10).
This study revealed that rs6710479 and rs7421861 in the PDCD1 gene confer susceptibility to PIU in Han Chinese. A stratified analysis showed that PDCD1/rs7565639 is associated with band keratopathy in PIU patients.
先前的研究表明，T 淋巴细胞凋亡异常与葡萄膜炎的发病机制有关。凋亡途径相关因子（包括 PDCD1、PDCD1LG2、FAS 和 FASLG）的遗传变异可能影响细胞凋亡，进而预测自身免疫性疾病的易感性。这在儿科特发性葡萄膜炎（PIU）和青少年特发性关节炎（JIA）相关性葡萄膜炎中尚未得到研究，因此这是本研究的主题。
使用 iPLEX Gold assay 和 MassARRAY 平台，对 1238 例 PIU 患者、128 例 JIA 相关性葡萄膜炎患者和 1114 名健康对照者的多个凋亡相关途径基因的 14 个单核苷酸多态性（SNP）进行分析。
与对照组相比，PIU 患者中 PDCD1/rs6710479 CC 基因型的频率较低（Pc=3.42×10）。PIU 患者中 PDCD1/rs7421861 A 等位基因的频率较高（Pc=4.85×10）。分层分析显示，角膜带状变性与 PDCD1/rs7565639 CT 基因型呈正相关（Pc=1.05×10），与 PDCD1/rs7565639 C 等位基因呈负相关（Pc=3.76×10）。
本研究表明，PDCD1 基因中的 rs6710479 和 rs7421861 赋予汉族人发生 PIU 的易感性。分层分析显示，PDCD1/rs7565639 与 PIU 患者的角膜带状变性有关。
