Evaluation of AQP4 functional variants and its association with fragile X-associated tremor/ataxia syndrome.
Evaluation of AQP4 functional variants and its association with fragile X-associated tremor/ataxia syndrome.
复制标题
DOI：
10.3389/fnagi.2022.1073258
复制
发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
脆性X相关性震颤/共济失调综合征（FXTAS，OMIM# 300623）是一种迟发性神经退行性疾病，伴有FMR 1前突变携带者（55-200 CGG）的发病率降低。FXTAS患者的临床症状通常开始于动作性震颤。之后，可能会出现不同的发现，包括共济失调，以及更不稳定的下肢远端感觉丧失和自主神经功能障碍，并逐渐进展。还观察到认知缺陷，包括记忆问题和执行功能缺陷，在一些个体中逐渐进展为痴呆。水通道蛋白4（Aquaporin 4，AQP 4）是一种广泛分布于中枢神经系统星形胶质细胞的水通道。AQP 4活性和表达的变化与几种中枢神经系统疾病有关。先前的研究表明AQP 4单核苷酸多态性（SNP）与脑水稳态和神经退行性疾病相关。迄今为止，FXTAS尚未研究这种关联。为了研究AQP 4 SNPs与FXTAS发病风险之间的关系，共选择了7种常见的AQP 4 SNPs，并对95名患有FXTAS的FMR 1前突变携带者和65名未患有FXTAS的FMR 1前突变携带者进行了基因分型。比较各组间AQP 4单倍型的频率，表示FXTAS组中26个杂合个体和5个纯合子为次要等位基因的携带者，而无FXTAS组中25个杂合个体和2个纯合子为次要等位基因的携带者。统计学分析显示AQP 4单核苷酸多态性/单倍型与FXTAS的发展之间没有显着关联。尽管AQP 4与多种脑部疾病有关，但其与FXTAS的关系仍不清楚。鉴定新的易患FXTAS或调节疾病进展的遗传标记对于未来涉及预测和治疗的研究至关重要。
Fragile X-associated tremor/ataxia syndrome (FXTAS, OMIM# 300623) is a late-onset neurodegenerative disorder with reduced penetrance that appears in adult FMR1 premutation carriers (55–200 CGGs). Clinical symptoms in FXTAS patients usually begin with an action tremor. After that, different findings including ataxia, and more variably, loss of sensation in the distal lower extremities and autonomic dysfunction, may occur, and gradually progress. Cognitive deficits are also observed, and include memory problems and executive function deficits, with a gradual progression to dementia in some individuals. Aquaporin 4 (AQP4) is a commonly distributed water channel in astrocytes of the central nervous system. Changes in AQP4 activity and expression have been implicated in several central nervous system disorders. Previous studies have suggested the associations of AQP4 single nucleotide polymorphisms (SNPs) with brain-water homeostasis, and neurodegeneration disease. To date, this association has not been studied in FXTAS. To investigate the association of AQP4 SNPs with the risk of presenting FXTAS, a total of seven common AQP4 SNPs were selected and genotyped in 95 FMR1 premutation carriers with FXTAS and in 65 FMR1 premutation carriers without FXTAS. The frequency of AQP4-haplotype was compared between groups, denoting 26 heterozygous individuals and 5 homozygotes as carriers of the minor allele in the FXTAS group and 25 heterozygous and 2 homozygotes in the no-FXTAS group. Statistical analyses showed no significant associations between AQP4 SNPs/haplotypes and development of FXTAS. Although AQP4 has been implicated in a wide range of brain disorders, its involvement in FXTAS remains unclear. The identification of novel genetic markers predisposing to FXTAS or modulating disease progression is critical for future research involving predictors and treatments.
影响因子：
4.6
作者：
Dadgostar E;Tajiknia V;Shamsaki N;Naderi-Taheri M;Aschner M;Mirzaei H;Tamtaji OR
通讯作者：
Tamtaji OR