Data_Sheet_1_UQCRC1 variants in early-onset and familial Parkinson's disease in a Taiwanese cohort.docx

BackgroundA recent Taiwanese study reported variants of the ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene linked to autosomal dominant parkinsonism with polyneuropathy. This study investigated the pathogenicity of UQCRC1 in a Taiwanese cohort of patients with Parkinson's disease (PD).
MethodThis study involved 107 participants (98 with early-onset PD and nine with familial PD). All UQCRC1 coding exons and exon–intron boundaries were sequenced. The rarity and pathogenicity of the identified variants were analyzed. The carrier frequencies of our cohort and the Taiwan Biobank were compared through a Pearson's χ2 or Fisher's exact test along with Bonferroni corrections.
ResultsThree missense variants (c.643G > C, p.D215H; c.800C > G, p.P267R, and c.923A > G, p.N308S) and seven rare variants were identified. No significant differences in the missense-variant carrier frequency were noted between our cohort and individuals in the Taiwan Biobank. Furthermore, no significant associations were noted between the variants and the risk of PD.
ConclusionsOur study is not supporting a role of UQCRC1 variants in PD.

研究背景 近期一项台湾地区的研究报道，泛醇-细胞色素c还原酶核心蛋白1（UQCRC1）基因的变异与伴多发性神经病的常染色体显性遗传性帕金森病相关。本研究针对台湾地区帕金森病（PD）患者队列，探究UQCRC1基因变异的致病性。
研究方法 本研究共纳入107名受试者，其中98例为早发性PD患者，9例为家族性PD患者。对UQCRC1基因的所有编码外显子及外显子-内含子边界区域进行测序。分析所鉴定变异的稀有性与致病性。通过Pearson卡方检验或Fisher精确检验结合邦费罗尼（Bonferroni）校正，比较本研究队列与台湾生物样本库（Taiwan Biobank）的变异携带频率。
研究结果 共鉴定出3个错义变异（c.643G > C，p.D215H；c.800C > G，p.P267R；c.923A > G，p.N308S）以及7个稀有变异。本研究队列与台湾生物样本库个体的错义变异携带频率无显著差异。此外，未观察到上述变异与PD发病风险存在显著关联。
研究结论 本研究结果不支持UQCRC1基因变异在帕金森病发病中发挥致病作用。