BMC Neurology (May 2021)

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

  • Chong-Yao Jin,
  • Ran Zheng,
  • Zhi-Hao Lin,
  • Nai-Jia Xue,
  • Ying Chen,
  • Ting Gao,
  • Yi-Qun Yan,
  • Yi Fang,
  • Ya-Ping Yan,
  • Xin-Zhen Yin,
  • Jun Tian,
  • Jia-Li Pu,
  • Bao-Rong Zhang

DOI
https://doi.org/10.1186/s12883-021-02215-7
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 7

Abstract

Read online

Abstract Background 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. Methods 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. Results 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). Conclusion An increased aggregate burden of the COL6A3 gene was detected in patients with PD.

Keywords