Brighina L, Frigerio R, Schneider N K, Lesnick T G, de Andrade M, Cunningham J M, Farrer M J, Lincoln S J, Checkoway H, Rocca W A, Maraganore D M
Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Neurology. 2008 Apr 15;70(16 Pt 2):1461-9. doi: 10.1212/01.wnl.0000304049.31377.f2. Epub 2008 Mar 5.
Aggregation and fibrillization of the alpha-synuclein protein (encoded by the SNCA gene) may represent key events in the pathogenesis of Parkinson disease (PD). Variability in the length of a dinucleotide repeat sequence (REP1) within the SNCA promoter confers susceptibility to sporadic PD. Pesticide exposures may also confer susceptibility to PD. Our objective was to test possible joint effects of SNCA REP1 genotypes and pesticide exposures on the risk of PD.
This was a case-control study. Cases were recruited prospectively from the Department of Neurology of the Mayo Clinic, Rochester, MN, after June 1, 1996. The control subjects included unaffected siblings of cases and unrelated population control subjects. We assessed pesticide exposures by telephone interview and genotyped SNCA REP1. Odds ratios (ORs) and 95% CIs were determined using conditional logistic regression models.
There were 833 case-control pairs. We observed an increased risk of PD with increasing SNCA REP1 bp length (OR, 1.18 for each score unit; 95% CI, 1.02-1.37; p = 0.03). Pesticide exposures were associated with PD in younger subjects only (lowest quartile of age at study, <or=59.8 years; OR, 1.80; 95% CI, 1.12-2.87; p = 0.01 for all pesticides; OR, 2.46; 95% CI, 1.34-4.52; p = 0.004 for herbicides). In multivariate analyses, both SNCA REP1 score and pesticide exposures were significantly associated with PD in younger subjects, but there were no pairwise interactions.
Our findings suggest that SNCA REP1 genotype and herbicides have independent effects on risk of Parkinson disease, primarily in younger subjects.
α-突触核蛋白（由SNCA基因编码）的聚集和纤维化可能是帕金森病（PD）发病机制中的关键事件。SNCA启动子内二核苷酸重复序列（REP1）长度的变异性赋予散发性PD易感性。农药暴露也可能导致PD易感性。我们的目的是测试SNCA REP1基因型和农药暴露对PD风险的可能联合作用。
这是一项病例对照研究。病例于1996年6月1日后从明尼苏达州罗切斯特市梅奥诊所神经科前瞻性招募。对照受试者包括病例的未受影响的兄弟姐妹和无关的人群对照受试者。我们通过电话访谈评估农药暴露情况，并对SNCA REP1进行基因分型。使用条件逻辑回归模型确定比值比（OR）和95%可信区间（CI）。
共有833对病例对照。我们观察到随着SNCA REP1碱基对长度增加，PD风险增加（每个评分单位的OR为1.18；95%CI为1.02 - 1.37；p = 0.03）。仅在较年轻的受试者中，农药暴露与PD相关（研究时年龄的最低四分位数，≤59.8岁；OR为1.80；95%CI为1.12 - 2.87；所有农药的p = 0.01；除草剂的OR为2.46；95%CI为1.34 - 4.52；p = 0.004）。在多变量分析中，SNCA REP1评分和农药暴露在较年轻的受试者中均与PD显著相关，但没有成对相互作用。
我们的研究结果表明，SNCA REP1基因型和除草剂对帕金森病风险有独立影响，主要在较年轻的受试者中。
