Hutter Carolyn M, Samii Ali, Factor Stewart A, Nutt John G, Higgins Donald S, Bird Thomas D, Griffith Alida, Roberts John W, Leis Berta C, Montimurro Jennifer S, Kay Denise M, Edwards Karen L, Payami Haydeh, Zabetian Cyrus P
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Eur J Neurol. 2008 Feb;15(2):134-9. doi: 10.1111/j.1468-1331.2007.02012.x. Epub 2007 Dec 18.
UCHL1 has been proposed as a candidate gene for Parkinson's disease (PD). A meta-analysis of white and Asian subjects reported an inverse association between the non-synonymous UCHL1 S18Y polymorphism and PD risk. However, this finding was not replicated in a large case-control study and updated meta-analysis restricted to white subjects. We performed a case-control study of 1757 PD patients recruited from movement disorder clinics and 2016 unrelated controls from four regions of the United States. All subjects self-reported as white. We did not observe evidence for an association between S18Y genotypes and PD (overall P-value for association: P = 0.42). After adjustment for age, sex, and recruitment region, the odds ratio for Y/S versus S/S was 0.91 (95% CI: 0.78-1.06) and for Y/Y versus S/S was 0.87 (95% CI: 0.58-1.29). We also did not observe a significant association for recessive or dominant models of inheritance, or after stratification by age at onset, age at blood draw, sex, family history of PD, or recruitment region. Our results suggest that UCHL1 S18Y is not a major susceptibility factor for PD in white populations although we cannot exclude the possibility that the S18Y variant exerts weak effects on risk, particularly in early-onset disease.
UCHL1已被提出作为帕金森病（PD）的候选基因。一项针对白人和亚洲受试者的荟萃分析报告称，非同义UCHL1 S18Y多态性与PD风险呈负相关。然而，这一发现并未在一项大型病例对照研究以及仅限于白人受试者的更新荟萃分析中得到重复验证。我们开展了一项病例对照研究，纳入了从运动障碍诊所招募的1757例PD患者以及来自美国四个地区的2016名无亲缘关系的对照。所有受试者均自我报告为白人。我们未观察到S18Y基因型与PD之间存在关联的证据（关联的总体P值：P = 0.42）。在对年龄、性别和招募地区进行调整后，Y/S与S/S相比的比值比为0.91（95%置信区间：0.78 - 1.06），Y/Y与S/S相比的比值比为0.87（95%置信区间：0.58 - 1.29）。我们也未观察到隐性或显性遗传模式存在显著关联，在按发病年龄、采血年龄、性别、PD家族史或招募地区进行分层后也未观察到显著关联。我们的结果表明，UCHL1 S18Y不是白人人群中PD的主要易感因素，尽管我们不能排除S18Y变异对风险产生微弱影响的可能性，尤其是在早发性疾病中。
