Study of GCH1 and TH genes in Chinese patients with Parkinson's disease.
Study of GCH1 and TH genes in Chinese patients with Parkinson's disease.
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中国帕金森病患者GCH1和TH基因的研究
DOI：
10.1016/j.neurobiolaging.2018.02.004
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发表时间：
2018
影响因子：
4.2
通讯作者：
Zhang Bao-Rong
中科院分区：
文献类型：
--
作者：
Yan Ya-Ping;Zhang Bo;Shen Ting;Si Xiao-Li;Guo Zhang-Yu;Tian Jun;Xu Cong-Ying;Zhang Bao-Rong
帕金森病（PD）患者的全外显子组测序显示，患者中GTP环化水解酶I（GCH1）变异的频率显著高于对照组，GCH1rs11158026也被发现增加PD的风险。为了研究多巴反应性肌张力障碍相关基因对PD的遗传贡献，在PD患者中检测了GCH 1和酪氨酸羟化酶（TH）。共招募了859名研究受试者，包括421名PD患者和438名对照。在1例临床诊断为PD的患者中检测到GCH 1基因的一种已知变异（c.239G > A，p.S80N）。在TH中，鉴定出3种杂合变体，c.1495G > A（p.V499M，rs1800033）、c.334 A > G（p.V112M，rs6356）和c.813 G > A（p.K271K，rs6357）。按年龄分层后，迟发性PD组rs6356G等位基因的频率显著低于对照组（p= 0.041）。本研究结果提示，在更大样本范围内筛选GCH 1和检测TH的rs6356，对分析多巴反应性肌张力障碍相关基因与PD的关系具有重要意义。
Whole-exome sequencing of Parkinson's disease (PD) patients has revealed that the frequency of GTP-cyclohydrolase I (GCH1) variants was significantly higher in patients than in controls.GCH1rs11158026 was also found to increase the risk of PD. To investigate genetic contribution of dopa-responsive dystonia–related genes to PD,GCH1, and tyrosine hydroxylase (TH) were tested in PD patients. A total of 859 study subjects comprising 421 patients with PD and 438 controls were recruited. ForGCH1gene, one known variant (c.239G > A, p.S80N) was detected in a patient who was diagnosed with PD clinically. In TH, 3 heterozygous variants, c.1495G > A (p. V499M, rs1800033), c.334 A > G (p.V112M, rs6356), and c.813 G > A (p. K271K, rs6357), were identified. After stratification by age, the frequency of rs6356G allele was significantly lower (p= 0.041) for the late-onset PD group than controls. Our results indicate that to analyze the relationship between dopa-responsive dystonia–related genes and PD, it is important to screenGCH1and test rs6356 of TH in a larger sample.