Abstract
Several epidemiologic studies have described an association between low serum uric acid (UA) and Parkinson disease (PD). Uric acid is a known antioxidant, and one proposed mechanism of neurodegeneration in PD is oxidative damage of dopamine neurons. However, other complex metabolic pathways may contribute. The purpose of this study is to elucidate potential mechanisms of low serum UA in PD. Subjects who met diagnostic criteria for definite or probable PD (n = 20) and controls (n = 20) aged 55–80 years were recruited. Twenty-four hour urine samples were collected from all participants, and both uric acid and allantoin were measured and corrected for body mass index (BMI). Urinary metabolites were compared using a twoway ANOVA with diagnosis and sex as the explanatory variables. There were no significant differences between PD and controls for total UA (p = 0.60), UA corrected for BMI (p = 0.37), or in the interaction of diagnosis and sex on UA (p = 0.24). Similarly, there were no significant differences between PD and controls for allantoin (p = 0.47), allantoin corrected for BMI (p = 0.57), or in the interaction of diagnosis and sex on allantoin (p = 0.78). Allantoin/UA ratios also did not significantly differ by diagnosis (p = 0.99). Our results imply that low serum UA in PD may be due to an intrinsic mechanism that alters the homeostatic set point for serum UA in PD, and may contribute to relatively lower protection against oxidative damage. These findings provide indirect support for neuroprotection trials aimed at raising serum UA.
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References
Albrecht E et al (2014) Metabolite profiling reveals new insights into the regulation of serum urate in humans. Metabolomics 10:141–151
Andreadou E et al (2009) Serum Uric Acid Levels in Patients with Parkinson’s disease: their relationship to treatment and disease duration. Clin Neurol Neurosurg 111:724–728
Becker M, Roessler B (1995) Hyperuricemia and gout. In: Scriver C, Beaudet A, Sly W, Valle D (eds) The metabolic and molecular basis of inherited disease, 5th edn. McGraw-Hill Book Company, New York, pp 1192–1202
Bierer D, Quebbemann A (1982) Effect of L-dopa on renal handling of uric acid. J Pharmacol Exp Ther 223:55–59
Church W, Ward V (1994) Observations on serum uric acid levels and the risk of idiopathic Parkinson’s disease. Brain Res Bull 33:419–424
Davis J, Grandinetti A, Waslien C, Ross G, White L, Morens D (1996) Observations on serum uric acid levels and the risk of idiopathic Parkinson’s disease. Am J Epidemiol 144:480–484
de Lau L, Koudstaal P, Hofman A, Breteler M (2005) Serum uric acid and the risk of Parkinson disease. Ann Neurol 58:797–800
Devgun M, Dhillon H (1992) Importance of diurnal variations on clinical value and interpretation of serum urate measurements. J Clin Pathol 45:110–113
Elbaz A, Moisan F (2008) Update in the epidemiology of Parkinson’s disease. Curr Opin Neurol 21:454–460
Gao X, Chen H, Choi H, Curhan G, Schwarzschild M, Ascherio A (2008) Diet, urate, and Parkinson’s disease risk in men. Am J Epidemiol 167:831–838
Gelb D, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. JAMA Neurol 56:33–39
Goetz C, Fahn S, Martinez-Martin P (2007) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): process, format, and clinimetric testing plan. Mov Disord 22:41–47
Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53:S26–S36
Jinnah H, Friedmann T (2000) Lesch-Nyhan disease and its variants. In: Scriver C, Beaudet A, Sly W, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 2537–2570
Jinnah H et al (2010) Attenuated variants of Lesch–Nyhan disease. Brain Res Bull 133:671–689
Kandiah N, Zhang A, Cenina A, Au W, Nadkarni N, Tan L (2014) Montreal cognitive assessment for the screening and prediction of cognitive decline in early Parkinson’s disease. Parkinsonism Relat Disord 20:1145–1148
Mikami T, Kita K, Tomita S, Qu G, Tasaki Y, Ito A (2000) Is allantoin in serum and urine a useful indicator of exercise-induced oxidative stress in humans? Free Radic Res 32:235–244
Puig J, Torres R, de Miguel E, Sánchez A, Bailén R, Banegas J (2012) Uric acid excretion in healthy subjects: a nomogram to assess the mechanisms underlying purine metabolic disorders. Metabolism 61:512–518
Schiess M, Oh I (2008) Serum uric acid and clinical progression in Parkinson disease: potential biomarker for nigrostriatal failure. Arch Neurol 65:698–699
Schwarzschild M et al (2008) Serum urate as a predictor of clinical and radiographic progression in Parkinson disease. Arch Neurol 65:716–723
Schwarzschild M et al (2014) Inosine to increase serum cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. JAMA Neurol 71:141–150
Shen C, Luo W, Lin C, Ding M (2013) Serum urate and the risk of Parkinson’s disease: results from a meta-analysis. Can J Neurol Sci 40:73–79
Simon K et al (2014) Mendelian randomization of serum urate and Parkinson disease progression. Ann Neurol 76:862–868
Sperling O (2006) Hereditary renal hypouricemia. Mol Genet Metab 89:14–18
Tolun A, Zhang H, Il’yasova D, Sztaray J, Young S, Millington D (2010) Allantoin in human urine quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Anal Biochem 401:191–193
Young S, Zhang Z, Corzo D, Bali D, Kishnani P, Millington D (2009) Long term monitoring of patients with infantile-onset Pompe disease on enzyme replacement therapy using a urinary glucose tetrasaccharide biomarker. Genet Med 11:536–541
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This work was supported in part by a grant from the NINDS at the NIH (P50 NS071669). Natasha Hakkal contributed to data collection and patient recruitment for this study.
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The authors report no financial disclosures or conflicts of interest pertaining to the work done in this study.
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Sampat, R., Young, S., Rosen, A. et al. Potential mechanisms for low uric acid in Parkinson disease. J Neural Transm 123, 365–370 (2016). https://doi.org/10.1007/s00702-015-1503-4
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DOI: https://doi.org/10.1007/s00702-015-1503-4