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, Jianshe East Road 1, Zhengzhou, 450052, People's Republic of China.
The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, People's Republic of China.
Hum Genomics. 2020 Dec 7;14(1):46. doi: 10.1186/s40246-020-00296-y.
Several studies have stated that TNF-α participates in the pathogenesis of scleritis, but also in several systemic autoimmune diseases and vasculitis, of which some are associated with scleritis. Earlier GWAS and SNP studies have confirmed that multiple SNPs of TNF related genes are associated with many immune-mediated disorders. The purpose of this study was to examine the association of TNF related gene polymorphisms with scleritis in Chinese Han. A case-control study was carried out in 556 non-infectious scleritis cases and 742 normal controls. A total of 28 single-nucleotide polymorphisms (SNPs) were genotyped by the iPLEXGold genotyping assay.
No significant correlations were seen between the individual SNPs in the TNF related genes and scleritis. Haplotype analysis showed a significantly decreased frequency of a TNFAIP3 TGT haplotype (order of SNPs: rs9494885, rs3799491, rs2230926) (Pc = 0.021, OR = 0.717, 95% CI = 0.563-0.913) and a significantly increased frequency of a TNFSF4 GT haplotype (order of SNPs: rs3850641, rs704840) (Pc = 0.004, OR = 1.691, 95% CI = 1.205-2.372) and TNFSF15 CCC haplotype (order of SNPs: rs6478106, rs3810936, rs7865494) (Pc = 0.012, OR = 1.662, 95% CI = 1.168-2.363) in patients with scleritis as compared with healthy volunteers.
This study reveals that a TGT haplotype in TNFAIP3 may be a protective factor for the development of scleritis and that a GT haplotype in TNFSF4 and a CCC haplotype in TNFSF15 may be risk factors for scleritis in Chinese Han.
多项研究表明 TNF-α 参与了巩膜炎的发病机制,但也参与了几种系统性自身免疫性疾病和血管炎,其中一些与巩膜炎有关。早期的 GWAS 和 SNP 研究已经证实,TNF 相关基因的多个 SNP 与许多免疫介导的疾病有关。本研究旨在探讨 TNF 相关基因多态性与中国汉族人群巩膜炎的关系。采用病例对照研究,共纳入 556 例非感染性巩膜炎患者和 742 例正常对照。采用 iPLEXGold 基因分型检测方法对 28 个单核苷酸多态性(SNP)进行基因分型。
TNF 相关基因的单个 SNP 与巩膜炎之间无显著相关性。单体型分析显示,TNFAIP3 TGT 单体型(SNP 顺序:rs9494885、rs3799491、rs2230926)的频率显著降低(Pc=0.021,OR=0.717,95%CI=0.563-0.913),而 TNFSF4 GT 单体型(SNP 顺序:rs3850641、rs704840)的频率显著升高(Pc=0.004,OR=1.691,95%CI=1.205-2.372)和 TNFSF15 CCC 单体型(SNP 顺序:rs6478106、rs3810936、rs7865494)(Pc=0.012,OR=1.662,95%CI=1.168-2.363)在巩膜炎患者中显著高于健康对照组。
本研究表明,TNFAIP3 中的 TGT 单体型可能是巩膜炎发生的保护因素,而 TNFSF4 中的 GT 单体型和 TNFSF15 中的 CCC 单体型可能是汉族人群巩膜炎的危险因素。