title: Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease.
abstract: The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case-control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel-Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR=1.212 for T allele, 95% CI=1.097-1.340, p-value=0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR=1.187 for T allele, 95% CI=1.058-1.332, p-value=0.004) and Asian samples (allelic model, pooled OR=1.293 for T allele, 95% CI=1.058-1.580, p-value=0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value=0.0149) and CHB (Chinese, p-value=0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, PR China; Key Laboratory of Stem Cells and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan, PR China. Electronic address: zhuzhigang_km@163.com.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhu
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Ai
authors.forename: Wen-Min
authors.initials: WM
authors.lastname: Wang
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Xiao
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017594:Publication Bias; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: ACMSD; AD; Alzheimer's disease; CI; Functional polymorphism; GBA; GWAS; MAPT; MCCC1; MTHFR; Meta-analysis; OR; PD; Parkinson's disease; SNCA; SNP; STK39; SYT11; aminocarboxymuconate semialdehyde decarboxylase; confidence interval; genome-wide association study; glucosidase beta acid; mRNA expression; methylcrotonoyl-CoA carboxylase 1 (alpha); methylenetetrahydrofolate reductase; microtubule-associated protein tau; odds ratio; rs1801133; serine threonine kinase 39; single nucleotide polymorphism; synaptotagmin XI; synuclein alpha