Department of Ophthalmology, The Second Affiliated Hospital of Fujian Medical University, Engineering Research Center of Assistive Technology for Visual Impairment, Fujian Province University, Quanzhou, 362000, People's Republic of China.
Department of Ophthalmology and Optometry, The School of Medical Technology and Engineering, Fujian Medical University, Jiaotong Road 88, Fuzhou, 350004, People's Republic of China.
Hum Genomics. 2023 Feb 13;17(1):9. doi: 10.1186/s40246-023-00459-7.
Protein kinase C delta (PRKCD) and caspase recruitment domain family member 9 (CARD9) are genes involved in B and T cell activation, and cytokine production, which are vital mechanisms underlying autoimmune disease development. This study aimed to explore the association of the PRKCD and CARD9 genes with Vogt-Koyanagi-Harada disease (VKH) disease. The case-control study was performed to in 912 patients with VKH and 878 normal controls. MassARRAY system, SHEsis online platform, real-time PCR, and enzyme-linked immunosorbent assay were used to detect genotyping, haplotyping, mRNA expression, and cytokine levels, respectively.
We found that rs74437127 C allele of PRKCD, rs3812555 CC genotype, and C allele of CARD9 were associated with increased susceptibility of VKH (Pc = 0.020, OR = 1.624; Pc = 2.04 × 10, OR = 1.810; Pc = 2.76 × 10, OR = 1.698, respectively). However, the rs74437127 T allele, and rs3812555 TC genotype and T allele were linked with decreased susceptibility to VKH (Pc = 0.020, OR = 0.616; Pc = 7.85 × 10, OR = 0.559; Pc = 2.76 × 10, OR = 0.589, respectively). PRKCD ATG and CARD9 GCTTA haplotypes decreased susceptibility to VKH (Pc = 3.11 × 10, OR = 0.594; Pc = 5.00 × 10, OR = 0.639, respectively). Functional studies on rs3812555 genotyped individuals revealed that CC carriers had significantly higher CARD9 mRNA expression and tumour necrosis factor-α production than TC/TT carriers (P = 1.00 × 10; P = 2.00 × 10, respectively).
We found an association between PRKCD rs74437127 and CARD9 rs3812555 polymorphisms and VKH susceptibility and revealed that the increased susceptibility of rs3812555 for VKH may be mediated by regulating CARD9 gene expression and the production of pro-inflammatory cytokines, such as TNF-α.
蛋白激酶 C 德尔塔（PRKCD）和衔接蛋白募集结构域家族成员 9（CARD9）是参与 B 和 T 细胞激活以及细胞因子产生的基因，而这些都是自身免疫性疾病发展的重要机制。本研究旨在探讨 PRKCD 和 CARD9 基因与 Vogt-小柳-原田病（VKH）之间的关系。该病例对照研究纳入了 912 名 VKH 患者和 878 名正常对照。采用 MassARRAY 系统、SHEsis 在线平台、实时 PCR 和酶联免疫吸附试验分别检测基因分型、单体型、mRNA 表达和细胞因子水平。
我们发现 PRKCD 的 rs74437127 等位基因 C、rs3812555CC 基因型和 CARD9 的 C 等位基因与 VKH 的易感性增加相关（Pc=0.020，OR=1.624；Pc=2.04×10，OR=1.810；Pc=2.76×10，OR=1.698）。然而，rs74437127 的 T 等位基因、rs3812555TC 基因型和 T 等位基因与 VKH 的易感性降低相关（Pc=0.020，OR=0.616；Pc=7.85×10，OR=0.559；Pc=2.76×10，OR=0.589）。PRKCD ATG 和 CARD9 GCTTA 单体型降低了 VKH 的易感性（Pc=3.11×10，OR=0.594；Pc=5.00×10，OR=0.639）。对 rs3812555 基因型个体进行的功能研究表明，CC 携带者的 CARD9mRNA 表达和肿瘤坏死因子-α产生水平显著高于 TC/TT 携带者（P=1.00×10；P=2.00×10）。
我们发现 PRKCDrs74437127 和 CARD9rs3812555 多态性与 VKH 易感性之间存在关联，并揭示了 rs3812555 增加 VKH 易感性可能是通过调节 CARD9 基因表达和产生促炎细胞因子（如 TNF-α）来介导的。
