Mitochondrial DNA variants modulate genetic susceptibility to Parkinson's disease in Han Chinese

• Published in: Neurobiology of disease Vol. 114; pp. 17 - 23
• Main Authors: Wu, Hong-Mei, Li, Ting, Wang, Zhen-Feng, Huang, Shi-Shi, Shao, Zi-Qiang, Wang, Ke, Zhong, Hai-Qing, Chen, Song-Fang, Zhang, Xiong, Zhu, Jian-Hong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2018; Elsevier
• Subjects: Aged; Asian Continental Ancestry Group - ethnology; Asian Continental Ancestry Group - genetics; Displacement loop; DNA, Mitochondrial - genetics; Female; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genetic Variation - genetics; Haplogroup; Humans; Male; Middle Aged; Mitochondrial DNA; Parkinson Disease - diagnosis; Parkinson Disease - ethnology; Parkinson Disease - genetics; Parkinson's disease; Variant; Variant; Haplogroup; Displacement loop; Mitochondrial DNA; Parkinson's disease
• DOI: 10.1016/j.nbd.2018.02.015
• ISSN: 0969-9961; 1095-953X

It is well recognized that mitochondrial dysfunction is involved in the pathogenesis of Parkinson's disease (PD). The mtDNA displacement loop (D-loop) region is known to accumulate structural alterations and mutations. To understand how mtDNA variants contribute to the susceptibility to sporadic PD in Chinese, a total of 500 PD patients and 505 controls were recruited from East China, and their D-loop regions were sequenced. A total of 389 variants were detected out of the 1005 subjects. There were 91 variants with frequencies >1%, which included 88 single nucleotide polymorphisms (SNPs), 2 deletions and 1 insertion. Amongst, 6 SNPs were significantly associated with sporadic PD. Specifically, the SNPs 151T/C, 189G/A, 16086C/T and 16271C/T contributed to increased susceptibility, while 318C/T and 16134T/C were associated with reduced risk for PD. Further analyses of mtDNA haplogroups and their risk for PD occurrence showed that subjects carrying haplogroup A5 were susceptible while haplogroup B5 carriers were more resistant to the disease. In summary, our study for the first time systematically analyzed mtDNA variants by sequencing the D-loop region in a Chinese population to understand their associations with PD. These results demonstrate that mtDNA variants modulate risk for sporadic PD. •First time analyses of mtDNA variants in PD by sequencing the D-loop region in an Asian population•6 SNPs out of 389 variants in the D-loop region exhibit significant association with PD.•A protective role of haplogroup B5 against PD is strengthened by multiple lines of analyses.•A potentially novel disease-promoting haplogroup A5 is identified.