C9orf72 mutation is rare in Alzheimer's disease, Parkinson's disease, and essential tremor in China.
GGGGCC repeat expansions in the C9orf72 gene have been identified as a major contributing factor in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Given the overlapping of clinical phenotypes and pathological characteristics between these two diseases and Alzheimer's disease (AD), Parkinson's disease (PD), and essential tremor (ET), we speculated regarding whether C9orf72 repeat expansions also play a major role in these three diseases. Using the repeat-primed polymerase chain reaction method, we screened for C9orf72 in three groups of patients with PD (n = 911), AD (n = 279), and ET (n = 152) in the Chinese Han population. There were no pathogenic repeats (>30 repeats) detected in either the patients or controls (n = 314), which indicated that the pathogenic expansions of C9orf72 might be rare in these three diseases. However, the analysis of the association between the number of repeats (p = 0.001), short/intermediate genotype (short: <7 repeats; intermediate: ≥7 repeats) (odds ratio 1.37 [1.05, 1.79]), intermediate/intermediate genotype (Odds ratio 2.03 [1.17, 3.54]), and PD risks indicated that intermediate repeat alleles could act as contributors to PD. To the best of our knowledge, this study is the first to reveal the correlation between C9orf72 and Chinese PD, AD, or ET patients. Additionally, the results of this study suggest the novel idea that the intermediate repeat allele in C9orf72 is most likely a risk factor for PD.
Department of Neurology, Xiangya Hospital, Central South University Changsha, China.
Bin
B
Jiao
Ji-Feng
JF
Guo
Ya-Qin
YQ
Wang
Xin-Xiang
XX
Yan
Lin
L
Zhou
Xiao-Yan
XY
Liu
Fu-Feng
FF
Zhang
Ya-Fang
YF
Zhou
Kun
K
Xia
Bei-Sha
BS
Tang
Lu
L
Shen
Alzheimer's disease; C9orf72; Parkinson's disease; essential tremor; risk factor