Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson's disease

• Published in: BMC neurology Vol. 21; no. 1; p. 187
• Main Authors: Jin, Chong-Yao, Zheng, Ran, Lin, Zhi-Hao, Xue, Nai-Jia, Chen, Ying, Gao, Ting, Yan, Yi-Qun, Fang, Yi, Yan, Ya-Ping, Yin, Xin-Zhen, Tian, Jun, Pu, Jia-Li, Zhang, Bao-Rong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.05.2021; BioMed Central; BMC
• Subjects: Age; COL6A3; Collagen; Development and progression; Dystonia; Gene; Gene frequency; Gene mutations; Genes; Genetic aspects; Genetic screening; Genomes; Health aspects; Movement disorders; Muscular dystrophy; Mutation; Neurodegenerative diseases; Neurological research; Parkinson's disease; Pathogenicity; Patients; Proteins; China; COL6A3; Dystonia; Gene; Parkinson’s disease
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-021-02215-7

To date, the genetic contribution to Parkinson's disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis. First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified 7 novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.038). An increased aggregate burden of the COL6A3 gene was detected in patients with PD.