Li Ting, Li He, Li Yue, Dong Shu-An, Yi Ming, Zhang Qiu-Xia, Feng Bin, Yang Li, Shi Fu-Dong, Yang Chun-Sheng
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China.
Front Genet. 2021 Jul 21;12:690537. doi: 10.3389/fgene.2021.690537. eCollection 2021.
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system and it is understandable that environmental and genetic factors underlie the etiology of NMOSD. However, the susceptibility genes and associated pathways of NMOSD patients who are AQP4-Ab positive and negative have not been elucidated.
Secondary analysis from a NMOSD Genome-wide association study (GWAS) dataset originally published in 2018 (215 NMOSD cases and 1244 controls) was conducted to identify potential susceptibility genes and associated pathways in AQP4-positive and negative NMOSD patients, respectively (132 AQP4-positive and 83 AQP4-negative).
In AQP4-positive NMOSD cases, five shared risk genes were obtained at chromosome 6 in AQP4-positive NMOSD cases by using more stringent -Values in both methods ( < 0.05/16,532), comprising CFB, EHMT2, HLA-DQA1, MSH5, and SLC44A4. Fifty potential susceptibility gene sets were determined and 12 significant KEGG pathways were identified. Sixty-seven biological process pathways, 32 cellular-component pathways, and 29 molecular-function pathways with a -Value of <0.05 were obtained from the GO annotations of the 128 pathways identified. In the AQP4 negative NMOSD group, no significant genes were obtained by using more stringent -Values in both methods ( < 0.05/16,485). The 22 potential susceptibility gene sets were determined. There were no shared potential susceptibility genes between the AQP4-positive and negative groups, furthermore, four significant KEGG pathways were also identified. Of the GO annotations of the 165 pathways identified, 99 biological process pathways, 37 cellular-component pathways, and 29 molecular-function pathways with a -Value of <0.05 were obtained.
The potential molecular mechanism underlying NMOSD may be related to proteins encoded by these novel genes in complements, antigen presentation, and immune regulation. The new results may represent an improved comprehension of the genetic and molecular mechanisms underlying NMOSD.
视神经脊髓炎谱系障碍（NMOSD）是一种中枢神经系统炎症性疾病，环境和遗传因素构成NMOSD的病因这一点是可以理解的。然而，水通道蛋白4抗体（AQP4-Ab）阳性和阴性的NMOSD患者的易感基因及相关通路尚未阐明。
对2018年最初发表的NMOSD全基因组关联研究（GWAS）数据集（215例NMOSD病例和1244例对照）进行二次分析，以分别确定AQP4阳性和阴性NMOSD患者中的潜在易感基因及相关通路（132例AQP4阳性和83例AQP4阴性）。
在AQP4阳性的NMOSD病例中，通过两种方法使用更严格的P值（<0.05/16,532），在6号染色体上获得了5个共同的风险基因，包括补体因子B（CFB）、组蛋白赖氨酸N-甲基转移酶2（EHMT2）、人类白细胞抗原-DQA1（HLA-DQA1）、错配修复蛋白5（MSH5）和溶质载体家族44成员4（SLC44A4）。确定了50个潜在的易感基因集，并鉴定出12条显著的京都基因与基因组百科全书（KEGG）通路。从鉴定出的128条通路的基因本体（GO）注释中获得了67条生物过程通路、32条细胞组分通路和29条分子功能通路，P值<0.05。在AQP4阴性的NMOSD组中，通过两种方法使用更严格的P值（<0.05/16,485）未获得显著基因。确定了22个潜在的易感基因集。AQP4阳性和阴性组之间没有共同的潜在易感基因，此外，还鉴定出4条显著的KEGG通路。在鉴定出的165条通路的GO注释中，获得了99条生物过程通路、37条细胞组分通路和29条分子功能通路，P值<0.05。
NMOSD潜在的分子机制可能与这些新基因编码的蛋白质在补体、抗原呈递和免疫调节中的作用有关。这些新结果可能代表了对NMOSD遗传和分子机制的更好理解。
