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.
Gene. 2013 Nov 15;531(1):78-83. doi: 10.1016/j.gene.2013.07.034. Epub 2013 Aug 3.
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.
MTHFR 是帕金森病（PD）的候选风险基因，该基因编码区的一个功能性 SNP（rs1801133）已在全球范围内广泛研究其与该疾病的关联，但总体结果不一致。在这里，为了评估 rs1801133 与一般人群中 PD 风险的关系，我们对欧洲和亚洲人群的所有可用病例对照样本进行了系统的荟萃分析，共纳入 1820 例 PD 病例和 7530 例健康对照，使用固定效应模型的 Mantel-Haenszel 方法计算 rs1801133 与 PD 的合并优势比（OR）和 95%置信区间（95%CI）。总体而言，rs1801133 与 PD 风险显著相关（等位基因模型，T 等位基因的合并 OR=1.212，95%CI=1.097-1.340，p 值=0.0002）。按种族分层时，在欧洲人群（等位基因模型，T 等位基因的合并 OR=1.187，95%CI=1.058-1.332，p 值=0.004）和亚洲人群（等位基因模型，T 等位基因的合并 OR=1.293，95%CI=1.058-1.580，p 值=0.012）中也观察到显著的关联。此外，rs1801133 还与 CEU（欧洲人，p 值=0.0149）和 CHB（中国人，p 值=0.0178）HapMap 人群中的 MTHFR mRNA 表达显著相关。综上所述，我们的荟萃分析表明，rs1801133 与欧洲和亚洲人群的 PD 易感性显著相关，MTHFR 可能是 PD 的一个真正的风险基因。
