Gout and the risk of Parkinson's disease in Denmark.
Gout and the risk of Parkinson's disease in Denmark.
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丹麦的痛风和帕金森病的风险。
DOI：
10.1007/s10654-013-9791-1
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发表时间：
2013
影响因子：
13.6
通讯作者：
Ritz,Beate
中科院分区：
文献类型：
--
作者：
Schernhammer,Eva;Qiu,Jiaheng;Wermuth,Lene;Lassen,ChristinaFunch;Friis,Soren;Ritz,Beate
越来越多的证据表明，氧化应激在帕金森病（PD）病因学中起着重要作用[1，2]。重要的是，尿酸在实验研究中已被证明对神经元具有抗氧化作用[3，4]。最近，几项观察性研究也评估了血清尿酸水平与PD风险之间的相关性，并一致报告血清尿酸水平最高的个体的PD风险较低[5-10]。高尿酸血症最常见的代谢紊乱是痛风。因此，如果高尿酸血症降低了PD的风险，痛风也应该与PD风险呈负相关。迄今为止，有两项研究评估了痛风与PD风险之间的相关性，两项研究均报告了负相关性[11，12]，尽管仅在其中一项研究中观察到男性中存在相关性[11]。使用丹麦人口登记，我们的目的是确认这两个以前的观察性研究的结果。我们调查了抗痛风处方药使用史是否与PD风险相关。根据丹麦全国范围内的住院和门诊医院登记记录，我们确定了4，484例在2001-2008年期间首次诊断为PD的患者，并根据丹麦国家处方登记处（DNPR）（记录了自1995年以来丹麦的所有处方）确认了PD用药史[13]。我们从丹麦民事登记系统中随机选择了22，416名人口对照[14]，按出生年份和性别进行密度匹配。我们从所有研究参与者的DNPR中提取了有关抗痛风药物使用的信息。暴露定义为病例在首次诊断PD之前或其匹配对照的相应日期（索引日期）之前至少接受过一次抗痛风药物处方。处方包括解剖治疗化学（ATC）组M04抗痛风制剂（M04 AA抑制尿酸生成的制剂（如别嘌呤醇）、M04 AB增加尿酸排泄的制剂（如苯溴马隆）、M04 AC对尿酸代谢无影响的制剂（如秋水仙碱）和M04 AX（其他抗痛风制剂，如尿酸氧化酶）。使用logistic回归模型估计比值比（OR），校正年龄、性别和慢性阻塞性肺疾病作为吸烟的指标。研究和方法的更多详细信息，包括研究人群的基线特征，已在其他地方提供[15]。我们发现抗痛风药物的使用与PD风险之间没有关联。这种关联的缺乏在PD发作时的性别或年龄方面没有差异（表1）。当我们排除PD病例时，
There is growing evidence that oxidative stress plays a major role in Parkinson’s disease (PD) etiology [1, 2]. Importantly, uric acid has been shown in experimental studies to have an antioxidant effect on neurons [3, 4]. Recently, several observational studies have also evaluated associations between serum uric acid levels and PD risk and have consistently reported a lower risk of PD among individuals with the highest levels of serum uric acid [5–10]. The most common metabolic disorder underlying hyper uricemia is gout. Thus, if hyperuricemia decreases the risk of PD, gout should also be negatively associated with PD risk. Two studies, to date, have evaluated the association between gout and PD risk and both reported an inverse association [11, 12], although the association was only observed among men in one of the two studies [11]. Using Danish population registers, we aimed to confirm the findings from these two previous observational studies. We investigated whether a history of use of anti-gout prescription medications was associated with PD risk. From nationwide Danish in-and outpatient Hospital Register records, we identified 4,484 patients with a first time diagnosis of PD between 2001–2008 and a diagnosis confirming PD medication history according to the Danish National Prescription Registry (DNPR) that records all prescription in Denmark since 1995 [13]. We randomly selected 22,416 population controls from the Danish Civil Registration System [14], density-matched by birth year and sex. We extracted information about the use of anti-gout drugs from the DNPR for all study participants. Exposure was defined as at least one prescription of anti-gout drugs prior to the first diagnosis of PD for the cases or the corresponding date (index date) for their matched controls. Prescriptions included Anatomical Therapeutic Chemical (ATC) group M04 anti-gout preparations (M04AA preparations inhibiting uric acid production (eg, allopurinol), M04AB preparations increasing uric acid excretion (eg, benzbromarone), M04AC preparations with no effect on uric acid metabolism (eg, colchicine), and M04AX (other anti-gout preparations, eg, urate oxidase). Odds ratios (OR) were estimated using logistic regression models adjusted for age, sex, and chronic obstructive pulmonary disease as an indicator of smoking. Further details of the study and methods, including baseline characteristics of the study population, have been provided elsewhere [15]. We found no associations between the use of anti-gout medications and risk of PD. This lack of an association did not differ by gender or age at onset of PD (Table 1). Results were similar when we excluded PD cases that