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Association of the COQ2 V393A Variant with Parkinson's Disease: A Case-Control Study and Meta-Analysis.

Yang X, Xi J, Zhao Q, Jia H, An R, Liu Z, Xu Y - PLoS ONE (2015)

Bottom Line: Subgroup analysis of our data showed that the V393A variant was significantly associated with early-onset PD (OR 3.71, 95%CI 1.51 to 9.15, p = 0.002) but not with late-onset disease (OR 1.65, 95%CI 0.69 to 3.95, p = 0.260).In conclusion, our findings show for the first time that the V393A variant in the COQ2 gene increases risk of PD among the population of east Asia.These results, combined with research on Japanese, lend genetic support to the hypothesis that oxidative stress underlies pathogenesis of both PD and MSA.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan Province, 610041, P.R. China.

ABSTRACT
Both Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases of uncertain etiology, but they show similarities in their pathology and clinical course. The fact that the gene encoding α-synuclein is associated with both diseases also suggests that they share some genetic determinants. Recent studies in Japan associating MSA with a variant in the COQ2 gene led us to question whether variants in the COQ2 gene are associated with PD in Han Chinese in a case-control study. A total of 564 patients with PD were genotyped using the ligase detection rection, together with 484 gender- and age-matched healthy subjects. The M128V and R387X variants of COQ2 were not detected in patients or controls; instead, we detected only the heterozygous V393A variant (CT genotype). The frequency of the CT genotype encoding the V393A mutation was significantly higher in patients PD (4.08%) than in controls (1.86%), corresponding to an odds ratio of 2.24 (95%CI 1.03 to 4.90, p = 0.037). The frequency of the C allele of the V393A variant was significantly higher in patients with PD than in controls (OR 2.22, 95%CI 1.02 to 4.82, p = 0.039), and this was also observed in a meta-analysis of studies from mainland China, Taiwan and Japan. Subgroup analysis of our data showed that the V393A variant was significantly associated with early-onset PD (OR 3.71, 95%CI 1.51 to 9.15, p = 0.002) but not with late-onset disease (OR 1.65, 95%CI 0.69 to 3.95, p = 0.260). Gender was not significantly associated with either genotype or minor allele frequencies. In conclusion, our findings show for the first time that the V393A variant in the COQ2 gene increases risk of PD among the population of east Asia. These results, combined with research on Japanese, lend genetic support to the hypothesis that oxidative stress underlies pathogenesis of both PD and MSA.

No MeSH data available.


Related in: MedlinePlus

Meta-analysis of the association between the COQ2 V393A variant and PD in different Asian populations.The Events column reports the number of patients with the CT genotype; the Total column, the total number of patients with CC and CT genotypes.CI, confidence interval; OR, odds ratio; PD, Parkinson’s disease.
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pone.0130970.g001: Meta-analysis of the association between the COQ2 V393A variant and PD in different Asian populations.The Events column reports the number of patients with the CT genotype; the Total column, the total number of patients with CC and CT genotypes.CI, confidence interval; OR, odds ratio; PD, Parkinson’s disease.

Mentions: This is the first study to confirm an association between PD and the COQ2 V393A variant. One study in Japan [8] and two from Taiwan [16,17] failed to detect this association, although they did find a trend towards higher frequency of the C allele in the PD group than in the control group: 2.5% vs. 1.6–2.2% in the Japanese study, and 1.6% vs. 0.94–1.1% in the Taiwanese work. When we meta-analyzed the data from these three studies with our own data using RevMan 5.2, we found the V393A variant to be significantly associated with risk of PD (p = 0.009; Fig 1). This suggests that an association may exist in Asian populations, but larger controlled studies are needed. At the same time, several studies suggest that this association may not exist in Caucasians. The Japanese study failed to detect the V393A variant in Europeans or North Americans [8], and a more recent study also failed to detect the variant in Europeans [18]; another European study detected the variant in only 1 of 1900 patients with PD, but not in any of 788 patients with MSA or 600 healthy controls [19]. Studies are therefore needed to clarify the relevance of this genetic association in Asians and non-Asians.


Association of the COQ2 V393A Variant with Parkinson's Disease: A Case-Control Study and Meta-Analysis.

Yang X, Xi J, Zhao Q, Jia H, An R, Liu Z, Xu Y - PLoS ONE (2015)

Meta-analysis of the association between the COQ2 V393A variant and PD in different Asian populations.The Events column reports the number of patients with the CT genotype; the Total column, the total number of patients with CC and CT genotypes.CI, confidence interval; OR, odds ratio; PD, Parkinson’s disease.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476583&req=5

pone.0130970.g001: Meta-analysis of the association between the COQ2 V393A variant and PD in different Asian populations.The Events column reports the number of patients with the CT genotype; the Total column, the total number of patients with CC and CT genotypes.CI, confidence interval; OR, odds ratio; PD, Parkinson’s disease.
Mentions: This is the first study to confirm an association between PD and the COQ2 V393A variant. One study in Japan [8] and two from Taiwan [16,17] failed to detect this association, although they did find a trend towards higher frequency of the C allele in the PD group than in the control group: 2.5% vs. 1.6–2.2% in the Japanese study, and 1.6% vs. 0.94–1.1% in the Taiwanese work. When we meta-analyzed the data from these three studies with our own data using RevMan 5.2, we found the V393A variant to be significantly associated with risk of PD (p = 0.009; Fig 1). This suggests that an association may exist in Asian populations, but larger controlled studies are needed. At the same time, several studies suggest that this association may not exist in Caucasians. The Japanese study failed to detect the V393A variant in Europeans or North Americans [8], and a more recent study also failed to detect the variant in Europeans [18]; another European study detected the variant in only 1 of 1900 patients with PD, but not in any of 788 patients with MSA or 600 healthy controls [19]. Studies are therefore needed to clarify the relevance of this genetic association in Asians and non-Asians.

Bottom Line: Subgroup analysis of our data showed that the V393A variant was significantly associated with early-onset PD (OR 3.71, 95%CI 1.51 to 9.15, p = 0.002) but not with late-onset disease (OR 1.65, 95%CI 0.69 to 3.95, p = 0.260).In conclusion, our findings show for the first time that the V393A variant in the COQ2 gene increases risk of PD among the population of east Asia.These results, combined with research on Japanese, lend genetic support to the hypothesis that oxidative stress underlies pathogenesis of both PD and MSA.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan Province, 610041, P.R. China.

ABSTRACT
Both Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases of uncertain etiology, but they show similarities in their pathology and clinical course. The fact that the gene encoding α-synuclein is associated with both diseases also suggests that they share some genetic determinants. Recent studies in Japan associating MSA with a variant in the COQ2 gene led us to question whether variants in the COQ2 gene are associated with PD in Han Chinese in a case-control study. A total of 564 patients with PD were genotyped using the ligase detection rection, together with 484 gender- and age-matched healthy subjects. The M128V and R387X variants of COQ2 were not detected in patients or controls; instead, we detected only the heterozygous V393A variant (CT genotype). The frequency of the CT genotype encoding the V393A mutation was significantly higher in patients PD (4.08%) than in controls (1.86%), corresponding to an odds ratio of 2.24 (95%CI 1.03 to 4.90, p = 0.037). The frequency of the C allele of the V393A variant was significantly higher in patients with PD than in controls (OR 2.22, 95%CI 1.02 to 4.82, p = 0.039), and this was also observed in a meta-analysis of studies from mainland China, Taiwan and Japan. Subgroup analysis of our data showed that the V393A variant was significantly associated with early-onset PD (OR 3.71, 95%CI 1.51 to 9.15, p = 0.002) but not with late-onset disease (OR 1.65, 95%CI 0.69 to 3.95, p = 0.260). Gender was not significantly associated with either genotype or minor allele frequencies. In conclusion, our findings show for the first time that the V393A variant in the COQ2 gene increases risk of PD among the population of east Asia. These results, combined with research on Japanese, lend genetic support to the hypothesis that oxidative stress underlies pathogenesis of both PD and MSA.

No MeSH data available.


Related in: MedlinePlus