Cai Shiya, Zhang Jun, Zhou Chunya, Shi Wenjian, Gao Yingying, Chang Rui, Tan Handan, Wang Qingfeng, Ye Xingsheng, Cao Qingfeng, Zhou Qingyun, Yang Peizeng, Hu Jianmin
Department of Ophthalmology, The Second Affiliated Hospital of Fujian Medical University, Engineering Research Center of Assistive Technology for Visual Impairment, Fujian Province University, Quanzhou, PR China; Department of Ophthalmology & Optometry, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, PR China.
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, PR China.
Exp Eye Res. 2022 Oct;223:109203. doi: 10.1016/j.exer.2022.109203. Epub 2022 Jul 31.
Cyclin-dependent kinases 4/6 (CDK4/6) and D1-type cyclins (CCND1) can regulate the pro-inflammatory functions of various cytokines during the inflammatory response. This study investigated the association between CDK4/6-CCND1 variants and susceptibility in patients with Behcet's disease (BD). This case-control study enrolled 542 patients with BD and 754 healthy controls. Fourteen tagged single nucleotide polymorphisms (tag SNPs) of the CDK4/6-CCND1 gene were genotyped using the Sequenom MassARRAY system and iPLEX® Pro assay. The results indicated that the frequency of the CDK6 rs2282983 TT genotype was higher in the BD group than the control group (Pc = 0.040, OR = 1.408, 95% CI = 1.124-1.765), and CDK6 rs2282983 CT and rs42034 AG were negatively associated with BD (Pc = 3.647 × 10, OR = 0.598, 95% CI = 0.471-0.758; Pc = 0.039, OR = 0.626, 95% CI = 0.459-0.852, respectively). Furthermore, statistical analysis showed that CDK6 rs2282983 TT and CT genotypes were significantly associated with skin lesions in patients with BD (Pc = 0.042, OR = 1.436, 95% CI = 1.130-1.824; Pc = 0.001, OR = 0.594, 95% CI = 0.461-0.764, respectively). This study suggests that the CDK6 loci rs2282983 and rs42034 might confer genetic susceptibility to BD in a Han Chinese population, which could provide new insights into the pathogenesis of BD.
细胞周期蛋白依赖性激酶4/6（CDK4/6）和D1型细胞周期蛋白（CCND1）可在炎症反应过程中调节多种细胞因子的促炎功能。本研究调查了CDK4/6 - CCND1基因变异与白塞病（BD）患者易感性之间的关联。这项病例对照研究纳入了542例BD患者和754例健康对照。使用Sequenom MassARRAY系统和iPLEX® Pro检测法对CDK4/6 - CCND1基因的14个标签单核苷酸多态性（tag SNPs）进行基因分型。结果表明，BD组中CDK6 rs2282983 TT基因型的频率高于对照组（Pc = 0.040，OR = 1.408，95% CI = 1.124 - 1.765），且CDK6 rs2282983 CT和rs42034 AG与BD呈负相关（分别为Pc = 3.647×10，OR = 0.598，95% CI = 0.471 - 0.758；Pc = 0.039，OR = 0.626，95% CI = 0.459 - 0.852）。此外，统计分析表明，CDK6 rs2282983 TT和CT基因型与BD患者的皮肤病变显著相关（分别为Pc = 0.042，OR = 1.436，95% CI = 1.130 - 1.824；Pc = 0.001，OR = 0.594，95% CI = 0.461 - 0.764）。本研究提示，CDK6基因座rs2282983和rs42034可能赋予汉族人群患BD的遗传易感性，这可为BD的发病机制提供新的见解。
