Genetic variability related to serum uric acid concentration and risk of Parkinson's disease.

BACKGROUND: Low serum uric acid (UA) levels have been associated with increased Parkinson's disease (PD) risk and accelerated disease progression. We analyzed the effect of polymorphisms in 9 genes influencing serum UA concentration on the risk of PD. METHODS: We genotyped SLC2A9 rs734553, ABCG2 rs2231142, SLC17A1 rs1183201, SLC22A11 rs17300741, SLC22A12 rs505802, GCKR rs780094, PDZK1 rs12129861, LRRC16A+SCGN rs742132, and SLC16A9 rs12356193 in 1061 PD patients and 754 controls. For each subject we calculated a cumulative genetic risk score (GRS), defined as the total number of PD-risk alleles (range, 2-15) associated to lower serum UA levels. Serum UA levels were measured in a subgroup of 365 PD cases and 132 controls. RESULTS: Serum UA levels were significantly lower in men with PD than in controls. Subjects (both men and women) carrying more than 9 risk alleles (third GRS tertile) had a 1.5 higher risk of developing PD than subjects with less than 8 risk alleles (first GRS tertile). An inverse correlation was observed between higher GRS and lower serum UA concentration in both men and women. CONCLUSIONS: Genetic variability influencing serum UA levels might modify susceptibility to PD.

Serum uric acid and risk of dementia in Parkinson's disease.

OBJECTIVE: Low serum uric acid (UA) levels have been associated with a worse cognitive function later in life and also with a higher risk and faster progression of Parkinson's disease (PD). Here we studied whether serum UA levels and the genetic variants related to its variability are associated with the presence of dementia in a cohort of patients with PD. METHODS: The study included 343 PD patients, which were examined for the presence of dementia according to the MDS Task Force criteria (level 1). The predominant PD phenotype and UPDRS-III and Hoehn-Yahr scales were recorded. Serum UA levels were determined in each participant. Genotyping of SLC2A9 rs734553, ABCG2 rs2231142, SLC17A1 rs1183201, SLC22A11 rs17300741, SLC22A12 rs505802, GCKR rs780094, PDZK1 rs12129861, LRRC16A + SCGN rs742132, and SLC16A9 rs12356193 was carried out by Taqman analysis. For each subject we calculated a cumulative genetic risk score (GRS), defined as the total number of risk alleles (range 2-15) associated to lower serum UA levels. RESULTS: 72 out of 343 PD patients (21%) presented dementia. Serum UA levels were not different between PD patients with or without dementia. No significant association was detected between any single SNP and the risk of PD-dementia. When we analyzed the combined effect of the eight SNPs using the cumulative GRS no significant association between the number of risk alleles and the risk of PD was observed. CONCLUSIONS: Our data suggest that serum UA levels have not a significant impact on the risk of dementia in PD.

Aproximación al diagnóstico de enfermedades hepáticas por el laboratorio clínico / Approach to the diagnosis of liver diseases by the clinical laboratory

Las pruebas de función hepática se emplean para detectar, diagnosticar específicamente, estimar la severidad, y monitorear el curso de la enfermedad hepática. La interpretación efectiva del panel de función hepática requiere un conocimiento de la fisiopatología subyacente y las características de las pruebas del panel. Utilizando un enfoque esquemático, se clasifican las alteraciones hepáticas en dos grandes categorías: 1) necrosis celular y 2) colestasis, y aplicando el panel de función hepática recomendado por The National Academy of Clinical Biochemistry y la American Association for the Study of Liver Diseases, se interpretan las principales pruebas y su utilidad para evaluar inicialmente las enfermedades hepáticas sospechadas o conocidas de acuerdo con su capacidad para detectar daño celular, falta de permeabilidad de vías biliares, metabolismo aniónico orgánico y síntesis proteica. Finalmente se hacen unas recomendaciones para la interpretación del panel de pruebas dentro del contexto clínico.