Huang Xuemei, Chen Peter C, Poole Charles
Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7025, USA.
Neurology. 2004 Jun 22;62(12):2198-202. doi: 10.1212/01.wnl.0000130159.28215.6a.
The link of the apolipoprotein (APOE) -epsilon4 allele to Alzheimer disease (AD) has led to studies investigating the role of apoE polymorphisms in Parkinson disease (PD). The authors hypothesized that any association between PD and APOE alleles and genotypes would be too small to be detected or precisely estimated by an individual case-controlled study.
The hypothesis was tested by systematic review and meta-analysis of results from case-control studies that provided clear clinical or pathologic criteria for PD and that reported APOE genotype frequencies. Published reports were obtained from MEDLINE, Biosis Previews, and ISI Web of Science searches, supplemented by citation analysis from retrieved articles. The authors estimated and compared prevalence odds ratios (OR) for PD in relation to each allele and genotype.
Twenty-two eligible studies were identified. There was no evidence of heterogeneity (p > 0.4) or publication bias (p > 0.2) for any allele or genotype. The estimated summary OR for one or more copies of each APOE allele was 1.20 for APOE-epsilon2 (95% CI, 1.02 to 1.42), 0.83 for APOE-epsilon3 (95% CI, 0.63 to 1.09), and 0.99 for APOE-epsilon4 (95% CI, 0.87 to 1.14).
Unlike Alzheimer disease, for which the APOE-epsilon4 allele increases the prevalence and the APOE-epsilon2 allele is protective, the authors' analysis shows the APOE-epsilon2 allele, but not the APOE-epsilon4 allele, to be positively associated with sporadic Parkinson disease.
载脂蛋白(APOE)-ε4等位基因与阿尔茨海默病(AD)的关联促使人们研究APOE基因多态性在帕金森病(PD)中的作用。作者推测,PD与APOE等位基因及基因型之间的任何关联都太小,以至于无法通过个体病例对照研究检测到或精确估计。
通过对病例对照研究结果进行系统评价和荟萃分析来验证该假设,这些研究提供了明确的PD临床或病理标准,并报告了APOE基因型频率。通过检索MEDLINE、Biosis Previews和ISI Web of Science获取已发表的报告,并通过对检索到的文章进行引文分析加以补充。作者估计并比较了PD与每个等位基因和基因型相关的患病率比值比(OR)。
共识别出22项符合条件的研究。对于任何等位基因或基因型,均无异质性证据(p>0.4)或发表偏倚证据(p>0.2)。每个APOE等位基因一个或多个拷贝的估计汇总OR为:APOE-ε2为1.20(95%CI,1.02至1.42),APOE-ε3为0.83(95%CI,0.63至1.09),APOE-ε4为0.99(95%CI,0.87至1.14)。
与APOE-ε4等位基因增加患病率而APOE-ε2等位基因具有保护作用的阿尔茨海默病不同,作者的分析表明APOE-ε2等位基因而非APOE-ε4等位基因与散发性帕金森病呈正相关。