A Variant in Genes of the NPY System as Modifier Factor of Machado-Joseph Disease in the Chinese Population.
A Variant in Genes of the NPY System as Modifier Factor of Machado-Joseph Disease in the Chinese Population.
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NPY系统基因变异作为中国人群马查多-约瑟夫病的修饰因素
DOI：
10.3389/fnagi.2022.822657
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发表时间：
2022
影响因子：
4.8
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Ding D;Chen Z;Wang C;Tang X;Zhang L;Fang Q;Qiu R;Jiang H
最近，NPY过表达已被提出可以减轻Machado-Joseph病（MJD）小鼠模型中的运动缺陷和神经病变，表明其在MJD发病机制中的神经保护作用。我们的目的是评估中国人群中NPY及其受体的SNPs与MJD易感性之间的关联。此外，我们研究了这些SNPs是否调节MJD的发病年龄（AO）。共有527名MJD患者和487名健康对照者参加了这项研究，并对NPY及其受体基因中的4个特定选择的SNP（rs 16139，rs3037354，rs 2234759和rs 11100494）进行了基因分型。在本研究中，使用显性模型的基因型频率和等位基因的分布在NPY 5 R揭示了MJD和对照组之间的显着差异（P = 0.048和P = 0.024，分别）。扩大样本量后，采用显性模型，两组间的基因型和等位基因分布差异有统计学意义（分别为P = 0.034、P = 0.046和P = 0.016）。其他三个SNPs的基因型和等位基因分布在MJD和对照组之间没有显着差异。所有选择的SNPs对MJD的AO没有显著影响。NPY 5 R基因rs 11100494与MJD易感性相关，提示NPY系统可能参与MJD的发病。我们的研究表明，MJD中存在其他遗传修饰因子，沿着CAG扩增和已知的遗传修饰因子，这可能有助于更好地了解MJD的发病机制。
Recently, NPY overexpression has been proposed to alleviate motor deficits and neuropathy in Machado-Joseph disease (MJD) mouse models, indicating its neuroprotective role in the pathogenesis of MJD. We aimed to evaluate the association between SNPs in NPY and its receptors and the susceptibility of MJD in the Chinese population. Moreover, we investigated whether these SNPs modulate the age at onset (AO) of MJD. In total, 527 MJD patients and 487 healthy controls were enrolled in the study, and four specific selected SNPs (rs16139, rs3037354, rs2234759, and rs11100494) in NPY and its receptor genes were genotyped. In this study, the genotypic frequency using the dominant model and the allelic distribution of rs11100494 in NPY5R revealed a significant difference between the MJD and control group during the first-stage analysis (P = 0.048 and P = 0.024, respectively). After we expanded the sample size, significant differences were observed between the two groups using the dominant model in genotypic and allelic distribution (P = 0.034, P = 0.046, and P = 0.016, respectively). No significant differences in genotypic and allelic distribution were found between the MJD and control groups for the other three SNPs. All selected SNPs had no significant effect on the AO of MJD. The association of rs11100494 in the NPY5R gene and susceptibility of MJD suggested that the NPY system might be implicated in the pathogenesis of MJD. Our study demonstrated the existence of other genetic modifiers in MJD, along with CAG expansion and known genetic modifier factors, which might lead to a better understanding of MJD pathogenesis.
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