Fang Hwa-Shin, Chao Chih-Ying, Wang Chun-Chieh, Fan Wen-Lang, Huang Po-Jung, Fung Hon-Chung, Wu Yih-Ru
Division of General Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
J Mov Disord. 2022 Jan;15(1):33-37. doi: 10.14802/jmd.21073. Epub 2021 Nov 17.
A meta-analysis of locus-based genome-wide association studies recently identified a relationship between AXIN1 and Parkinson's disease (PD). Few studies of Asian populations, however, have reported such a genetic association. The influences of rs13337493, rs758033, and rs2361988, three PD-associated genetic variants of AXIN1, were investigated in the present study because AXIN1 is related to Wnt/β-catenin signaling.
A total of 2,418 individuals were enrolled in our Taiwanese cohort for analysis of the genotypic and allelic frequency. Polymerase chain reaction-restriction fragment length polymorphism analysis was employed for rs13337493 genotyping, and the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA) was used for rs758033 and rs2361988 genotyping in 672 patients with PD and 392 controls. Taiwan Biobank data of another 1,354 healthy controls were subjected to whole-genome sequencing performed using Illumina platforms at approximately 30× average depth.
Our results revealed that rs758033 {odds ratios [OR] (95% confidence interval [CI]) = 0.267 [0.064, 0.795], p = 0.014} was associated with the risk of PD, and there was a trend toward a protective effect of rs2361988 (OR [95% CI] = 0.296 [0.071, 0.884], p = 0.026) under the recessive model. The TT genotype of rs758033 (OR [95% CI] = 0.271 [0.065, 0.805], p = 0.015) and the CC genotype of rs2361988 (OR [95% CI] = 0.305 [0.073, 0.913], p = 0.031) were less common in the PD group than in the non-PD group.
Our findings indicate that the rs758033 and rs2361988 polymorphisms of AXIN1 may affect the risk of PD in the Taiwanese population.
基于位点的全基因组关联研究的一项荟萃分析最近确定了AXIN1与帕金森病(PD)之间的关系。然而,很少有针对亚洲人群的研究报道这种基因关联。由于AXIN1与Wnt/β-连环蛋白信号传导相关,因此在本研究中调查了AXIN1的三个与PD相关的基因变异rs13337493、rs758033和rs2361988的影响。
共有2418名个体纳入我们的台湾队列,用于分析基因型和等位基因频率。采用聚合酶链反应-限制性片段长度多态性分析对rs13337493进行基因分型,并使用Agena MassARRAY平台(美国加利福尼亚州圣地亚哥的Agena Bioscience公司)对672例PD患者和392名对照进行rs758033和rs2361988基因分型。另外1354名健康对照的台湾生物银行数据使用Illumina平台进行全基因组测序,平均深度约为30×。
我们的结果显示,rs758033 {优势比[OR](95%置信区间[CI])= 0.267 [0.064, 0.795],p = 0.014}与PD风险相关,并且在隐性模型下,rs2361988有保护作用的趋势(OR [95% CI] = 0.296 [0.071, 0.884],p = 0.026)。rs758033的TT基因型(OR [95% CI] = 0.271 [0.065, 0.805],p = 0.015)和rs2361988的CC基因型(OR [95% CI] = 0.305 [0.073, 0.913],p = 0.031)在PD组中比非PD组中更少见。
我们的研究结果表明,AXIN1的rs758033和rs2361988多态性可能影响台湾人群患PD的风险。