Mendelian randomization of serum urate and parkinson disease progression.
Mendelian randomization of serum urate and parkinson disease progression.
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DOI：
10.1002/ana.24281
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发表时间：
2014-12
影响因子：
11.2
通讯作者：
Ascherio, Alberto
中科院分区：
文献类型：
--
作者：
Simon, Kelly Claire;Eberly, Shirley;Gao, Xiang;Oakes, David;Tanner, Caroline M.;Shoulson, Ira;Fahn, Stanley;Schwarzschild, Michael A.;Ascherio, Alberto
较高的血清尿酸浓度预示着帕金森病（PD）患者更有利的预后。本研究的目的是使用孟德尔随机化方法检验这种关联的因果关系。该研究是在DATATOP和PRECEPT两项早期PD患者随机试验的参与者中进行的。808名有可用DNA的患者进行了三个SLC2A9单核苷酸多态性的基因分型，确定了与低尿酸浓度相关的等位基因，以及其他编码尿酸转运蛋白的基因中选定的snp，这些基因对血清尿酸水平影响不大或没有影响。根据三个SLC2A9位点的次要等位基因总数创建SLC2A9评分。主要结局是需要多巴胺能治疗的残疾。有4个或更多SLC2A9小等位基因的个体血清尿酸浓度比有2个或更少SLC2A9小等位基因的个体低0.69mg/dL （p = 0.0002）。随着SLC2A9评分的增加，发展为需要多巴胺能治疗的残疾的风险比（HR）增加（HR=1.16； 95%可信区间1.00 ~ 1.35;p= 0.056）。在比较分析中，0.5 mg/dL遗传导致的血清尿酸降低的HR为1.27(1.00至1.61,p= 0.0497)， 0.5 mg/dL测定的血清尿酸降低的HR为1.05（1.01至1.10,p=0.0133）。未发现与尿酸相关的其他不影响血清尿酸和PD进展的基因多态性之间存在关联。这种孟德尔随机化分析增加了高尿酸水平的因果保护作用的证据。
Higher serum urate concentrations predict more favorable prognosis in individuals with Parkinson disease (PD). The purpose of this study was to test the causality of this association using a mendelian randomization approach. The study was conducted among participants in DATATOP and PRECEPT, two randomized trials among patients with early PD. The 808 patients with available DNA were genotyped for three SLC2A9 single nucleotide polymorphisms that identify an allele associated with lower urate concentrations, and for selected SNPs in other genes encoding urate transporters that have modest or no effect on serum urate levels. A SLC2A9 score was created based on the total number of minor alleles at the three SLC2A9 loci . Primary outcome was disability requiring dopaminergic treatment. Serum urate concentrations were 0.69mg/dL lower among individuals with 4 or more SLC2A9 minor alleles as compared to those with two or less (p = 0.0002). The hazard ratio (HR) for progression to disability requiring dopaminergic treatment increased with increasing SLC2A9 score (HR=1.16; 95% confidence interval 1.00 to 1.35; p=.056). In a comparative analysis, the HR was 1.27 (1.00 to 1.61; p =0.0497) for a 0.5 mg/dL genetically conferred decrease in serum urate, and 1.05 (1.01 to 1.10; p=0.0133) for a 0.5 mg/dL decrease in measured serum urate. No associations were found between polymorphisms in other genes associated with urate that do not affect serum urate and PD progression. This Mendelian randomization analysis adds to the evidence of a causal protective effect of high urate levels.
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影响因子：
3.7
作者：
Schumacher T;Krohn M;Hofrichter J;Lange C;Stenzel J;Steffen J;Dunkelmann T;Paarmann K;Fröhlich C;Uecker A;Plath AS;Sommer A;Brüning T;Heinze HJ;Pahnke J
通讯作者：
Pahnke J
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
4
作者：
Do, Tuan Minh;Noel-Hudson, Marie-Sophie;Bourasset, Fanchon
通讯作者：
Bourasset, Fanchon
影响因子：
--
作者：
Schwarzschild, Michael A.;Schwid, Steven R.;Ascherio, Alberto
通讯作者：
Ascherio, Alberto
影响因子：
12.6
作者：
Gao J;Xu H;Huang X;Chen H
通讯作者：
Chen H