新型 SNARE 复合物多态性与多发性硬化症相关：多发性硬化症中的突触病迹象。
Novel SNARE Complex Polymorphisms Associated with Multiple Sclerosis: Signs of Synaptopathy in Multiple Sclerosis.
机构信息
Clinic of Neurology, İstanbul Training and Research Hospital, İstanbul, Turkey
Department of Medical Biology, Muğla Sıtkı Koçman University School of Medicine, Muğla, Turkey
出版信息
Balkan Med J. 2019 May 10;36(3):174-178. doi: 10.4274/balkanmedj.galenos.2018.2017.1034. Epub 2018 Dec 24.
BACKGROUND
It is well known that axonal degeneration plays a role in disability in patients with multiple sclerosis, and synaptopathy has recently become an important issue.
AIMS
To investigate the possible roles of selected synaptic and presynaptic membrane protein genetic polymorphisms (VAMP2, SNAP-25, synaptotagmin, and syntaxin 1A) in patients with multiple sclerosis.
STUDY DESIGN
Case-control study.
METHODS
A total of 123 patients with multiple sclerosis and 192 healthy controls were included. The functional polymorphisms of specific SNARE complex proteins (VAMP2, synaptotagmin XI, syntaxin 1A, and SNAP-25) were analyzed by polymerase chain reaction.
RESULTS
Significant differences were detected in the genotype and allele distribution of 26-bp Ins/Del polymorphisms of VAMP2 between patients with multiple sclerosis and control subjects; Del/Del genotype and Del allele of VAMP2 were more frequent in patients with multiple sclerosis (p=0.011 and p=0.004, respectively). Similarly, Ddel polymorphism of SNAP-25 gene C/C genotype (p=0.059), syntaxin 1A T/C and C/C genotypes (p=0.005), and synaptotagmin XI gene C allele (p=0.001) were observed more frequently in patients with multiple sclerosis. CC, syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes, and synaptotagmin XI gene were found to be associated with an increased risk for multiple sclerosis (p=0.012). Similarly, GC haplotype for rs3746544 of SNAP-25 gene and rs1051312 of SNAP-25 gene were associated with an increased risk for multiple sclerosis (p=0.022).
CONCLUSION
Genetic polymorphisms of SNARE complex proteins, which have critical roles in synaptic structure and communication, may play a role in the development of multiple sclerosis.
背景
众所周知，轴突变性在多发性硬化症患者的残疾中起作用，突触病最近已成为一个重要问题。
目的
研究选定的突触前膜蛋白遗传多态性（VAMP2、SNAP-25、突触结合蛋白和突触素 1A）在多发性硬化症患者中的可能作用。
研究设计
病例对照研究。
方法
共纳入 123 例多发性硬化症患者和 192 例健康对照者。通过聚合酶链反应分析特定 SNARE 复合物蛋白（VAMP2、突触结合蛋白 XI、突触素 1A 和 SNAP-25）的功能多态性。
结果
多发性硬化症患者与对照组之间 VAMP2 26-bpIns/Del 多态性的基因型和等位基因分布存在显著差异；多发性硬化症患者中 Del/Del 基因型和 Del 等位基因更为常见（p=0.011 和 p=0.004）。同样，SNAP-25 基因 C/C 基因型的 Ddel 多态性（p=0.059）、突触素 1A T/C 和 C/C 基因型（p=0.005）以及突触结合蛋白 XI 基因 C 等位基因（p=0.001）在多发性硬化症患者中更为常见。CC、rs1569061 突触素 1A 基因 33-bp 启动子区 TC 单倍型和突触结合蛋白 XI 基因与多发性硬化症的发病风险增加相关（p=0.012）。同样，SNAP-25 基因 rs3746544 的 GC 单倍型和 SNAP-25 基因 rs1051312 与多发性硬化症的发病风险增加相关（p=0.022）。
结论
在突触结构和通讯中起关键作用的 SNARE 复合物蛋白的遗传多态性可能在多发性硬化症的发病机制中起作用。
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