title: Association of the COQ2 V393A variant with risk of multiple system atrophy in East Asians: a case-control study and meta-analysis of the literature.
abstract: Recent studies in Japan have associated multiple system atrophy (MSA), a neurodegenerative disease of uncertain etiology, with polymorphism in the COQ2 gene. This led us to explore whether the same polymorphism is associated with MSA in Han Chinese and more broadly in East Asians. We conducted a case-control study with 82 Han Chinese with probable MSA and 484 gender- and age-matched healthy subjects, genotyping them using the ligase detection reaction. The results were meta-analyzed together with data from four previous studies to gain a broader picture of possible disease associations in East Asian populations. The COQ2 variants M78V and R337X were not detected in our Han Chinese patients or controls; only the heterozygous V393A variant (CT genotype) was detected. The frequency of this genotype was significantly higher in patients (7.3%) than in controls (1.86%; OR 4.17, 95% CI 1.44-12.04, p = 0.004). Subgroup analysis among patients showed a significant association of V393A with MSA involving cerebellar signs (MSA-C; OR 4.59, 95% CI 1.36-15.48, p = 0.007), but not with MSA involving parkinsonism (MSA-P). Meta-analysis of our results in Han Chinese with data from case-control studies in Japan, Korea, mainland China and Taiwan showed a significant association of V393A with MSA (OR 2.05, 95% CI 1.29-3.25, p = 0.002), which subgroup analysis showed to be significant for MSA-C (OR 2.75, 95% CI 1.98-3.84, p < 0.001) but not for MSA-P (OR 1.25, 95% CI 0.64-2.46, p = 0.51). These findings provide evidence that the previously reported association of COQ2 V393A polymorphism with increased risk of MSA in Japanese also applies to Han Chinese, as well as more broadly to other East Asian populations. This association may be particularly strong for MSA-C.
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: QuanZhen
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Xinglong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: SiJia
authors.initials: S
authors.lastname: Tian
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: An
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors.forename: JinHua
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China. neuroxym999@163.com.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000368:Aged; D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007564:Japan; D007723:Korea; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000453:epidemiology* / Q000235:genetics*; D012306:Risk; D013624:Taiwan
chemical_list: D019883:Alkyl and Aryl Transferases; C021386:4-hydroxybenzoate polyprenyltransferase
keywords: COQ2; Coenzyme Q10; Gene polymorphism; Multiple system atrophy