α-syn and SNP rs356219 as a potential biomarker in blood for Parkinson's disease in Mexican Mestizos.

Clinical criteria diagnose Parkinson's disease (PD), therefore, it is crucial to find biological elements that could support diagnosis or even act as prognostic tools of PD. The SNCA gene codifies a protein called α - synuclein; several studies associate genetic and biochemical factors of SNCA with PD, including transcript and plasmatic protein levels, however, contradictory evidence indicates inconclusive results. We aim to compare SNCA mRNA expression, plasmatic α-syn protein and rs356219 SNP between PD cases and a control group, and to identify a potential biomarker in Mexican mestizos', focusing on these three components determined in blood. We included 88 PD patients and 88 age-matched controls. We observed higher α-syn protein and decreased SNCA mRNA levels in PD subjects, compared to control group (p = 0.044 and p < 0.001, respectively). A statistically significant difference was found in allelic and genotypic frequencies of SNP rs356219 between PD patients and normal subjects (p = 0.006 and p = 0.023, respectively). Logistic regression analysis determined as optimal predictors of PD the GG genotype of SNP rs356219 (OR 2.49; p = 0.006) in a recessive model and α-syn protein (OR 1.057; p = 0.033). Furthermore, the G allele of SNP rs356219 was associated with higher plasmatic α-syn and mRNA levels in PD subjects. The receiver operating curves (ROC) distinguished PD from healthy controls with good sensitivity and specificity considering the plasmatic α-syn protein (AUC = 0.693, Sensitivity = 66.7 %, Specificity = 63.9 %) or a predictive probability of plasmatic α-syn protein and SNP rs356219 in a single model (AUC = 0.692, Sensitivity = 62.3 %, Specificity = 62.5 %). The performance of this classifier model in PD at early stage (n = 31) increase the discriminant power in both, plasmatic α-syn protein (AUC = 0.779, Sensitivity = 72.7 %, Specificity = 73.9 %) and predictive probability (AUC = 0.707, Sensitivity = 63.6 %, Specificity = 62.5 %). We propose that α-syn protein and SNP rs356219 together may work as a good signature of PD, and they can be suggested as a non-invasive biomarker of PD risk.

Toxoplasma gondii infection in pregnant women: a cross-sectional study in Matehuala City, Mexico.

OBJECTIVES: This study aimed to determine the seroprevalence of Toxoplasma gondii (T. gondii) infection in pregnant women in Matehuala City, Mexico; and the associated risk factors. DESIGN: A cross-sectional study. SETTING: Matehuala City, Mexico. PARTICIPANTS: 311 pregnant women. PRIMARY AND SECONDARY OUTCOME MEASURES: Sera of women were analysed for anti-T. gondii IgG and IgM antibodies by commercially available immunoassays. Bivariate and multivariate analyses were used to assess the association between T. gondii seroprevalence and the characteristics of the pregnant women. RESULTS: Thirteen (4.2%) of the 311 pregnant women studied were positive for anti-T. gondii IgG antibodies. No anti-T. gondii IgM antibodies were found in anti-T. gondii IgG seropositive women. No association between seropositivity and history of blood transfusion, transplantation, caesarean sections, deliveries, miscarriages or number of pregnancies was found. Logistic regression analysis of sociodemographic, behavioural and housing variables showed that availability of potable water at street represented a risk factor for T. gondii infection (age-adjusted OR=2.18; 95% CI: 1.05 to 4.53; p=0.03), whereas being born in Mexico was a protective factor for infection (age-adjusted OR=0.01; 95% CI: 0.001 to 0.35; p=0.008). CONCLUSIONS: In this first study on the seroepidemiology of T. gondii infection in pregnant women in Matehuala, we conclude that the seroprevalence of T. gondii infection is low and similar to those reported in pregnant women in other Mexican cities. However, the seroprevalence found is lower than those reported in pregnant women in other countries in the Americas and Europe. Two risk factors associated with T. gondii infection were identified. Results of the present study may help for the optimal planning of preventive measures against toxoplasmosis in pregnant women.

rs3764435 Associated With Parkinson's Disease in Mexican Mestizos: Case-Control Study Reveals Protective Effects Against Disease Development and Cognitive Impairment.

Parkinson's disease (PD) is the second most common movement disorder. Genetic risk factors provide information about the pathophysiology of PD that could potentially be used as biomarkers. The ALDH1A1 gene encodes for the aldehyde dehydrogenase enzyme, which is involved in the disposal of toxic metabolites of dopamine. Due to the cytotoxic nature of aldehydes, their detoxification is essential for cellular homeostasis. It has been reported that ALDH1A1 expression levels and activity are decreased in PD patients. A deficit in ALDH1A1 activity in the substantia nigra, may lead to the accumulation of neurotoxic aldehydes and eventually the cell death seen in PD. One of the single nucleotide polymorphisms (SNP) that may modulate ALDH1A1 activity levels is rs3764435 (A/C). To investigate whether a statistical association exists between PD and the SNP rs3764435, we carried out a population-based Case-Control association study (120 PD patients and 178 non-PD subjects) in Mexican mestizos. DNA was extracted from blood samples and genotyped for rs3764435 using real-time PCR. A significant difference was found between PD cases and controls in both allelic and genotypic frequencies. The calculated OR showed that the C/C genotype is a protective factor under the codominant and recessive models of inheritance. However, after stratifying by sex, the protective role of this genotype is conserved only in men. Also, under the codominant and dominant models, rs3764435 appears to exert a protective effect against cognitive impairment in PD patients. Here for the first time, we show an association between PD and rs3764435 in a Mexican mestizo population, suggesting it confers neuroprotection for dementia in PD and is neuroprotective against developing PD in the males of this population. While analysis of the SNP looks favorable, replication of our study in cell lines or rs3764435 KO mice is required to validate these results.

H1/H2 MAPT haplotype and Parkinson's disease in Mexican mestizo population.

Parkinson's disease (PD) is characterized by bradykinesia, resting tremor, rigidity and postural instability as well as early symptoms. Previous studies that evaluated the association between H1/H2 MAPT haplotype and PD were mostly conducted in European populations in which the H1 haplotype was a reported risk factor for PD. Despite those findings, some studies have suggested that the association may be ethnically dependent. Since studies conducted in Latin American population have been scarce, we genotyped the H1/H2 MAPT haplotype in Mexican mestizo population as part of a PD case-control study. DNA was extracted from peripheral blood leucocytes in 108 cases and 108 controls and detection of the H1/H2 haplotypes was achieved by determining the MAPT_238 bp deletion/insertion variant at intron 9 through end-point PCR followed by visual 3% agarose gel electrophoresis interpretation. We observed no-association between genotypes and PD risk [OR/CI (Odds ratio/95% Confidence Interval) of 1.60 (0.78-3.29) for H1/H2 genotype and 2.26 (0.20-25.78) for H2/H2]. No-association was maintained when stratifying our groups by central (p = 0.27) and northern regions (p = 0.70). Our data suggest that H1/H2 MAPT haplotype is not a risk factor to PD in our population.

Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population.

BACKGROUND: Cholesterol has been associated as a risk factor for cardiovascular disease. Recently, however, there is growing evidence about crucial requirement of neuron membrane cholesterol in the organization and function of the 5-HT1A serotonin receptor. For this, low cholesterol level has been reported to be associated with depression and suicidality. However there have been inconsistent reports about this finding and the exact relationship between these factors remains controversial. Therefore, we investigated the link between serum cholesterol and its fractions with depression disorder and suicide attempt in 467 adult subjects in Mexican mestizo population. METHODS: Plasma levels of total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) were determined in 261 MDD patients meeting the DSM-5 criteria for major depressive disorder (MDD), 59 of whom had undergone an episode of suicide attempt, and 206 healthy controls. RESULTS: A significant decrease in total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglyceride serum levels was observed in the groups of MDD patients and suicide attempt compared to those without suicidal behavior (p < 0.05). After adjusting for covariates, lower cholesterol levels were significantly associated with MDD (OR 4.229 CI 95% 2.555 - 7.000, p<.001) and suicide attempt (OR 5.540 CI 95% 2.825 - 10.866, p<.001) CONCLUSIONS: These results support the hypothesis that lower levels of cholesterol are associated with mood disorders like MDD and suicidal behavior. More mechanistic studies are needed to further explain this association.

Association between Blood Lead Levels and Delta-Aminolevulinic Acid Dehydratase in Pregnant Women.

Blood lead levels (BLLs) and delta-aminolevulinic acid dehydratase (ALAD) activity are considered biomarkers of lead exposure and lead toxicity, respectively. The present study was designed to investigate the association between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of 633 pregnant women aged 13-43 years participated in this study. Blood lead was measured by a graphite furnace atomic absorption spectrometer. ALAD activity was measured spectrophotometrically. Mean blood lead was 2.09 ± 2.34 µg/dL; and 26 women (4.1%) crossed the Centers for Disease Control (CDC) recommended level of 5 µg/dL. ALAD activity was significantly lower in women with levels of lead ≥5 µg/dL compared to those with BLLs < 5 µg/dL (p = 0.002). To reduce the influence of extreme values on the statistical analysis, BLLs were analyzed by quartiles. A significant negative correlation between blood lead and ALAD activity was observed in the fourth quartile of BLLs (r = -0.113; p < 0.01). Among women with blood lead concentrations ≥2.2 µg/dL ALAD activity was negatively correlated with BLLs (r = -0.413; p < 0.01). Multiple linear regression demonstrated that inhibition of ALAD in pregnant women may occur at levels of lead in blood above 2.2 µg/dL.

The relationship between blood lead levels and occupational exposure in a pregnant population.

BACKGROUND: Pregnant women exposed to lead are at risk of suffering reproductive damages, such as miscarriage, preeclampsia, premature delivery and low birth weight. Despite that the workplace offers the greatest potential for lead exposure, there is relatively little information about occupational exposure to lead during pregnancy. This study aims to assess the association between blood lead levels and occupational exposure in pregnant women from Durango, Mexico. METHODS: A cross-sectional study was carried out in a population of 299 pregnant women. Blood lead was measured in 31 women who worked in jobs where lead is used (exposed group) and 268 who did not work in those places (control group). Chi-square test was applied to compare exposed and control groups with regard to blood lead levels. Odds ratio (OR) and 95% confidence intervals (CI) were calculated. Multivariable regression analysis was applied to determine significant predictors of blood lead concentrations in the exposed group. RESULTS: Exposed women had higher blood lead levels than those in the control group (4.00 ± 4.08 µg/dL vs 2.65 ± 1.75 µg/dL, p = 0.002). Furthermore, women in the exposed group had 3.82 times higher probability of having blood lead levels ≥ 5 µg/dL than those in the control group. Wearing of special workwear, changing clothes after work, living near a painting store, printing office, junkyard or rubbish dump, and washing the workwear together with other clothes resulted as significant predictors of elevated blood lead levels in the exposed group. CONCLUSIONS: Pregnant working women may be at risk of lead poisoning because of occupational and environmental exposure. The risk increases if they do not improve the use of protective equipment and their personal hygiene.

Arsenic exposure and risk of preeclampsia in a Mexican mestizo population.

BACKGROUND: Exposure to arsenic in drinking water has been associated with various complications of pregnancy including fetal loss, low birth weight, anemia, gestational diabetes and spontaneous abortion. However, to date, there are no studies evaluating its possible association with preeclampsia. METHODS: This case-control study involved 104 preeclamptic and 202 healthy pregnant women. The concentrations of arsenic in drinking water and urine were measured using a Microwave Plasma-Atomic Emission Spectrometer. RESULTS: We found relatively low levels of arsenic in household tap water (range of 2.48-76.02 µg/L) and in the urine of the participants (7.1 µg/L vs 6.78 µg/L in cases and controls, respectively). CONCLUSIONS: The analysis between groups showed for the first time that at these lower levels of exposure there is no association with preeclampsia.

Relationship between blood lead levels and hematological indices in pregnant women.

Several studies have revealed a negative association between blood lead levels and hematological impairment. In this cross-sectional study, we examined the relationship between blood lead levels and hematological indices in 292 pregnant women from Durango, Mexico. Apparently healthy pregnant women, aged 14-41 years and at 3-41 weeks of gestation, were recruited between June 2007 and May 2008. Blood lead and hematological indices were measured. The mean blood lead was 2.79 ± 2.16 µg/dL, and lead levels ≥ 5 µg/dL were detected in 25 women (8.6%). Hemoglobin, hematocrit, and red blood cells count were significantly higher in pregnant women with a blood lead concentration of ≥ 5 µg/dL than the group with lower blood lead levels (p < .05). Mean corpuscular volume and mean corpuscular hemoglobin were not significantly related to lead levels. Hemoglobin and hematocrit showed a non-significant positive correlation with blood lead, but the correlation between red blood cell count and blood lead levels was statistically significant (r = 0.185, p = .002). The findings suggest that a positive association between blood lead and some hematological indices may occur at relatively low blood lead concentration (mean < 5 µg/dL).

Genetic variation in oxidative stress and DNA repair genes in a Mexican population.

BACKGROUND: Oxidative stress has been associated with several complex diseases. Effects generated as a result of oxidative stress may be modulated by various genes. Variation in these genes, particularly when located within coding or regulating regions, may be the primary cause of this modulation. The aim of this work was to determine the allelic and genotypic frequencies of CAT C-262T, SOD3 Ala58Thr, APEX1 Asp148Glu, XPD Lys751Gln and XRCC3 Thr241Met genetic markers in a northern Mexican population. SUBJECTS AND METHODS: This study analysed 250 unrelated individuals by RT-PCR. RESULTS: A high allele mutant frequency was found in SOD3 Ala58Thr and APEX1 Asp148Glu genetic markers (0.395 and 0.38, respectively). A correspondence analysis showed that northern Mexicans are close to European populations. A linkage disequilibrium test between XPD Lys751Gln and CAT C-262T and XPD Lys751Gln and SOD3 Ala58Thr genetic markers was significant (p = 0.000). CONCLUSION: The genetic markers described in this work will be a valuable resource for future functional studies in the northern Mexican population to explore comprehensively their role in the aetiology of human diseases. Furthermore, it will be necessary to replicate these studies in other regions of Mexico due to differences between Mexican sub-populations.

Propiedades psicométricas de la CES-D/IS en población universitaria de la ciudad de Durango, México / Psychometric properties of CES-D/IS in university population in Durango city, México

Introduction Depression has been frequently related with suicidal behavior. Evidences of depressive symptoms in adolescents and young people with suicidal ideation or suicidal intention have been showed in several studies. For that reason, it is necessary to have an adequate instrument to measure and identify some characteristics associated with self-destructive behavior in university students. Objective To evaluate the psychometric properties of CES-D/IS in students at the University Juarez of the State of Durango (UJED). Material and Methods The universe of study selected for the schooling period of 2008 consisted of 943 students from 13 academic units. CES-D/IS scale was applied. Before the interview informed consent was obtained from all the participants and they were informed about the nature and scope of the study. Exploratory factor analysis was conducted to evaluate the instrument validity, and Cronbach alpha for internal consistency. Further analysis included Student t-test and Mann-Withney U test. A p-value below 0.05 was considered to indicate statistical significance. The data were analyzed with SPSS, version 15 and R v 2.7.2. Results The total scale showed a high value of internal consistency (α=0.89), and similar results for academic areas, for age and sex. Factor analysis showed a four-factor structure that accounted for 45.5% of variance Conclusions CES-D/IS scale has adequate psychometric properties in reliability and in validity.

Introducción La depresión es un aspecto que constantemente se ha relacionado con la conducta suicida. La sintomatología depresiva ha sido evidenciada en varios estudios donde ha estado presente en adolescentes y jóvenes con pensamientos e intentos de suicidio. Por esta razón es de suma prioridad e interés el contar con un instrumento válido y confiable para la identificación y la medición de características relacionadas con la conducta autodestructiva en estudiantes universitarios. Objetivo Evaluar las propiedades psicométricas de la CES-D/IS, mediante su aplicación a estudiantes de nivel licenciatura de la Universidad Juárez del estado de Durango (UJED). Material y métodos El estudio incluyó a 943 estudiantes de 13 unidades académicas durante el periodo escolarizado de 2008. Se aplicó la escala CES-D/ IS. Se solicitó a los participantes el consentimiento informado y se les aseguró el manejo confidencial de los datos. Para medir la validez del instrumento se utilizó el análisis factorial exploratorio, se evaluó la consistencia interna mediante el coeficiente alfa de Cronbach, se emplearon estadísticos descriptivos, t de Student y U de Mann-Whitney para inferencias al 0.05. Los datos se procesaron con los paquetes estadísticos SPSS v15 y R v 2.7.2. Resultados La escala presentó una consistencia interna de α=0.89. El índice resultó homogéneo cuando se analizó por área de estudio, edad y sexo. El análisis factorial mostró cuatro factores con el 45.5% de la varianza explicada. Conclusiones La escala CES-D/IS, presentó buenas propiedades tanto en su confiabilidad como en su validez.

Blood lead levels and risk factors in pregnant women from Durango, Mexico.

In this cross-sectional study the authors determined blood lead levels (BLLs) and some risk factors for lead exposure in pregnant women. Two hundred ninety-nine pregnant women receiving medical attention by the Secretary of Health, State of Durango, Mexico, participated in this study between 2007 and 2008. BLLs were evaluated with graphite furnace atomic absorption spectrometry. The authors used Student t test, 1-way analysis of variance (ANOVA), and linear regression as statistical treatments. BLLs ranged from 0.36 to 23.6 µg/dL (mean = 2.79 µg/dL, standard deviation = 2.14). Multivariate analysis showed that the main predictors of BLLs were working in a place where lead is used, using lead glazed pottery, and eating soil.