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.
Keywords: COQ2; Coenzyme Q10; Gene polymorphism; Multiple system atrophy.