Age-Dependent Changes in Glutathione-S-Transferase: Correlation with Total Plasma Antioxidant Potential and Red Cell Intracellular Glutathione

The correlation between antioxidant capacity and oxidative damage during aging has been reported in several tissues in different species. Glutathione-S-transferases (GST) can metabolise endogenous and exogenous toxins and carcinogens by catalysing the conjugation of diverse electrophiles with reduced glutathione (GSH). We observe a significant (P < 0.001) increase in plasma GST activity as a function of human age (r = 0.5675). A significant (P < 0.001) positive correlation (r = 0.8979) is observed between GST activity and total plasma antioxidant potential measured as ferric reducing ability of the plasma (FRAP). GST activity and red cell intracellular GSH also show a significant positive correlation (r = 0.7014). We hypothesize that the increased activity of plasma GST is a manifestation of increased generation of ROS and a concomitant decrease in the level of plasma antioxidant capacity during aging

Lrrk2 p.Q1111H substitution and Parkinson's disease in Latin America

Fil: Mata, Ignacio F. Veterans Affairs Puget Sound Health Care System, Seattle, Washington; Estados Unidos.Fil: Wilhoite, Greggory J. Mayo Clinic College of Medicine. Department of Neuroscience, Jacksonville, Florida; Estados Unidos.Fil: Yearout, Dora. Veterans Affairs Puget Sound Health Care System, Seattle, Washington; Estados Unidos. Mayo Clinic College of Medicine. Department of Neuroscience, Jacksonville, Florida; Estados Unidos.Fil: Bacon, Justin A. Mayo Clinic College of Medicine. Department of Neuroscience, Jacksonville, Florida; Estados Unidos.Fil: Cornejo-Olivas, Mario. Mayo Clinic College of Medicine. Department of Neuroscience, Jacksonville, Florida; Estados Unidos.Fil: Mazzetti, Pilar. Mayo Clinic College of Medicine. Department of Neuroscience, Jacksonville, Florida; Estados Unidos.Fil: Marca, Victoria. Mayo Clinic College of Medicine. Department of Neuroscience, Jacksonville, Florida; Estados Unidos.Fil: Ortega, Olimpio. Universidad Nacional Mayor de San Marcos. School of Medicine, Lima; Perú.Fil: Acosta, Oscar. Instituto Nacional de Ciencias Neurológicas. Movement disorders, Lima; Perú.Fil: Cosentino, Carlos. Instituto Nacional de Ciencias Neurológicas. Movement disorders, Lima; Perú.Fil: Torres, Luis. Universidad Nacional del Altiplano, Puno; Perú.Fil: Medina, Angel C. University of Chile. Faculty of Medicine. ICBM. Molecular and Clinical Pharmacology, Santiago; Chile.Fil: Perez-Pastene, Carolina. University of Chile. Faculty of Medicine. ICBM. Molecular and Clinical Pharmacology, Santiago; Chile.Fil: Díaz-Grez, Fernando. Mayo Clinic College of Medicine. Department of Neuroscience, Jacksonville, Florida; Estados Unidos.Fil: Vilariño-Güell, Carles. Liga del Parkinson de Chile; Chile.Fil: Venegas, Pablo. Liga del Parkinson de Chile; Chile.Fil: Miranda, Marcelo. Liga del Parkinson de Chile; Chile.Fil: Trujillo-Godoy, Osvaldo. Hospital Barros Luco Trudeau; Chile.Fil: Layson, Luis. Hospital Barros Luco Trudeau; Chile.Fil: Avello, Rodrigo. Hospital Regional de Concepción; Chile.Fil: Dieguez, Elena. Universidad de la República. Facultad de Medicina. Departamento de Neurología, Montevideo; Uruguay.Fil: Raggio, Victor. Universidad de la República. Facultad de Medicina. Departamento de Genética, Montevideo; Uruguay.Fil: Micheli, Federico E. ANLIS Dr.C.G.Malbrán; Argentina.Fil: Perandones, Claudia. ANLIS Dr.C.G.Malbrán. Dirección Científico Técnica; Argentina.Fil: Alvarez, Victoria. Hospital Universitario Central de Asturias. Instituto de Investigación Nefrológica (IRSINFRIAT). Laboratorio de Genética Molecular, Oviedo; España.Fil: Segura-Aguilar, Juan. Instituto Nacional de Ciencias Neurológicas. Unidad de Neurogenética, Lima; Perú.Fil: Farrer, Matthew J. Mayo Clinic College of Medicine. Department of Neuroscience, Jacksonville, Florida; Estados Unidos.Fil: Zabetian, Cyrus P. Veterans Affairs Puget Sound Health Care System, Seattle, Washington; Estados Unidos.Fil: Ross, Owen A. Mayo Clinic College of Medicine. Department of Neuroscience, Jacksonville, Florida; Estados Unidos.Mutations in the LRRK2 gene are the most common genetic cause of Parkinson's disease, with frequencies displaying a high degree of population-specificity. Although more than 100 coding substitutions have been identified, only seven have been proven to be highly penetrant pathogenic mutations. Studies however are lacking in non-white populations. Recently, Lrrk2 p.Q1111H (rs78365431) was identified in two affected Hispanic brothers and absent in 386 non-Hispanic white healthy controls. We therefore screened this variant in 1460 individuals (1150 PD patients and 310 healthy controls) from 4 Latin American countries (Peru, Chile, Uruguay and Argentina). In our case-control series from Peru and Chile we observed an increased frequency of Lrrk2 p.Q1111H in patients (7.9%) compared to controls (5.4%) although the difference did not reach significance (OR 1.38; p = 0.10). In addition, the frequency of Lrrk2 p.Q1111H varied greatly between populations and further screening in a set of pure Amerindian and pure Spanish controls suggested that this variant likely originated in an Amerindian population. Further studies in other Latin American populations are warranted to assess its role as a risk factor for Parkinson's disease. Screening in Parkinson's disease patients from under-represented populations will increase our understanding of the role of LRRK2 variants in disease risk worldwide

Epidemiological, Clinical, and Molecular Study of a Cohort of Italian Parkinson Disease Patients: Association with Glutathione-S-Transferase and DNA Repair Gene Polymorphisms

Parkinson's disease (PD) is one of the most common neurodegenerative disorders whose etiology is multifactorial including both hereditary and environmental factors. Currently, pathogenic mutations in at least five genes have been implicated in familial PD generally accounting for less than 10\ua0% of all PD cases in most populations. It has been suggested that polymorphisms in other genes such as those encoding enzymes involved in oxidative metabolism and detoxification could be involved in predisposition to PD since oxidative stress in dopaminergic neurons is thought to be of central importance in the pathogenesis of the disease. The aim of our work was to study the association of genetic polymorphisms in genes involved in oxidative metabolism and detoxification mechanism, namely GSTM1, GSTT1, GSTP1, and those involved in DNA damage repair, OGG1 and XRCC1, in an Italian cohort of sporadic PD patients. We did not detect any association between GSTT1 and GTTM1 null polymorphisms and PD, whereas the 104GSTP1 polymorphism was associated with PD in male patients but not in females. Furthermore, we detected a protective effect of wild type genotype of XRCC1 in women