Ada Sandoval-Carrillo

Lack of association between Toxoplasma gondii infection and hypertensive disorders in pregnancy: a case–control study in a Northern Mexican population

BackgroundThe outcome of pregnancy is often threatened by hypertension disorders, i.e. eclampsia. Rate of infection with the protozoan parasite Toxoplasma gondii can be as high as 80% in pregnant women, and infection acquired during pregnancy can lead to fetal death. Very little is known about a potential association between infections, i.e. those with Toxoplasma gondii, and hypertensive disorders during pregnancy.MethodsThrough a case–control study design, we investigated the presence of anti-Toxoplasma IgG and anti-Toxoplasma IgM antibodies in 146 pregnant women suffering from hypertensive disorders (cases) and 146 age-matched normotensive pregnant women (controls) attending a public hospital in Durango City, Mexico. Obstetric and blood pressure characteristics from cases and controls were also obtained.ResultsSeroprevalence of anti-Toxoplasma IgG antibodies and IgG titers did not differ significantly in controls (8/146; 5.5%) and cases (9/146; 6.2%). Anti-Toxoplasma IgM antibodies were found in 2 (1.2%) controls and none of the cases. Seroprevalence of T. gondii in controls (5.5%) was similar to seroprevalences found in patients with mild preeclampsia (4/27: 14.8%), severe preeclampsia (5/95: 5.3%), eclampsia (0/16: 0%) and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) (0/8: 0%) (P = 0.23).ConclusionsOur results suggest that latent infection with T. gondii is not associated with hypertensive disorders in pregnant women in Northern Mexico. Further studies with larger sample sizes are needed to elucidate the association of infection with T. gondii with hypertensive disorders in pregnancy.

Association of COMT G675A and MTHFR C677T polymorphisms with hypertensive disorders of pregnancy in Mexican mestizo population

OBJECTIVE To investigate the relationship between COMT G675A and MTHFR C677T polymorphisms and hypertension disorders of pregnancy (HDP) in a Mexican mestizo population. DESIGN AND METHODS This case-control study involved 194 HDP and 194 normoevolutive pregnant women. The polymorphisms were genotyped by real time PCR. RESULTS Our results showed that the COMT AA genotype increases the risk to HDP (OR: 2.67; 95% CI 1.33-5.35), preeclampsia (OR: 2.69; 95% CI 1.00-7.22) and gestational hypertension (OR: 3.87; 95% CI 1.25-12.0). Furthermore, the double mutant genotype (COMTAA/MTHFRTT) potency the risk to HDP more than two times (OR: 5.21; 95% CI 1.12-24.3, p=0.019). CONCLUSION Our work provides evidence that COMT 675AA genotype is a risk factor for HDP and that this risk is increased by the presence of MTHFR 677TT genotype in a Mexican mestizo population.

Polymorphisms in DNA Repair Genes (APEX1, XPD, XRCC1 and XRCC3) and Risk of Preeclampsia in a Mexican Mestizo Population

Variations in genes involved in DNA repair systems have been proposed as risk factors for the development of preeclampsia (PE). We conducted a case-control study to investigate the association of Human apurinic/apyrimidinic (AP) endonuclease (APEX1) Asp148Glu (rs1130409), Xeroderma Pigmentosum group D (XPD) Lys751Gln (rs13181), X-ray repair cross-complementing group 1 (XRCC) Arg399Gln (rs25487) and X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphisms with PE in a Mexican population. Samples of 202 cases and 350 controls were genotyped using RTPCR. Association analyses based on a χ2 test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each polymorphism. The allelic frequencies of APEX1 Asp148Glu polymorphism showed statistical significant differences between preeclamptic and normal women (p = 0.036). Although neither of the polymorphisms proved to be a risk factor for the disease, the APEX1 Asp148Glu polymorphism showed a tendency of association (OR: 1.74, 95% CI = 0.96–3.14) and a significant trend (p for trend = 0.048). A subgroup analyses revealed differences in the allelic frequencies of APEX1 Asp148Glu polymorphism between women with mild preeclampsia and severe preeclampsia (p = 0.035). In conclusion, our results reveal no association between XPD Lys751Gln, XRCC Arg399Gln and XRCC3 Thr241Met polymorphisms and the risk of PE in a Mexican mestizo population; however, the results in the APEX1 Asp148Glu polymorphism suggest the need for future studies using a larger sample size.

Implications of DNA Methylation in Parkinson’s Disease

It has been 200 years since Parkinson’s disease (PD) was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation may be altered in response to some of these factors; therefore, it is proposed that epigenetic mechanisms, particularly DNA methylation, can have a fundamental role in gene–environment interactions that are related with PD. Epigenetic changes in PD-associated genes are now widely studied in different populations, to discover the mechanisms that contribute to disease development and identify novel biomarkers for early diagnosis and future pharmacological treatment. While initial studies sought to find associations between promoter DNA methylation and the regulation of associated genes in PD brain tissue, more recent studies have described concordant DNA methylation patterns between blood and brain tissue DNA. These data justify the use of peripheral blood samples instead of brain tissue for epigenetic studies. Here, we summarize the current data about DNA methylation changes in PD and discuss the potential of DNA methylation as a potential biomarker for PD. Additionally, we discuss environmental and nutritional factors that have been implicated in DNA methylation. Although the search for significant DNA methylation changes and gene expression analyses of PD-associated genes have yielded inconsistent and contradictory results, epigenetic modifications remain under investigation for their potential to reveal the link between environmental risk factors and the development of PD.

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.

Abstract 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.

Changes in the theta band coherence during motor task after hand immobilization

Many different factors can temporarily or permanently impair movement and impairs cortical organization, e.g. hand immobilization. Such changes have been widely studied using electroencephalography. Within this context, we have investigated the immobilization effects through the theta band coherence analysis, in order to find out whether the immobilization period causes any changes in the inter and intra-hemispheric coherence within the cerebral cortex, as well as to observe whether the theta band provides any information about the neural mechanisms involved during the motor act. We analyzed the cortical changes that occurred after 48 hours of hand immobilization. The theta band coherence was study through electroencephalography in 30 healthy subjects, divided into two groups (control and experimental). Within both groups, the subjects executed a task involving flexion and extension of the index finger, before and after 48 hours. The experimental group, however, was actually submitted to hand immobilization. We were able to observe an increase in the coupling within the experimental group in the frontal, parietal and temporal regions, and a decrease in the motor area. In order to execute manual tasks after some time of movement restriction, greater coherence is present in areas related to attention, movement preparation and sensorimotor integration processes. These results may contribute to a detailed assessment of involved neurophysiological mechanism in motor act execution.

TNF-α POLYMORPHISMS AND MATERNAL DEPRESSION IN A MEXICAN MESTIZO POPULATION

BACKGROUND Depressive disorders are common during pregnancy. There is compelling evidence that the inflammatory response system is important in the pathophysiology of depression. Higher concentrations of proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α) in depressed subjects have been described. Because several polymorphisms in the TNF-α promoter region are known to affect its gene expression, the aim of this study was determine whether TNF-α - 857C/T, -308G/A, and -238G/A polymorphisms confer susceptibility to depression during pregnancy in a Mexican mestizo population. METHODS This case-control study involved 153 depressed pregnant women and 177 controls. Polymorphisms were genotyped using real-time PCR. Odds ratios (OR) and 95% confidence intervals adjusted by age, body mass index, number of pregnancies, months of pregnancy and number of abortions were used to estimate risk. RESULTS The -857CT genotype was found to increase the risk for depression (OR= 1.73, 95% CI= 1.06-2.82). In contrast, the -238GA genotype reduced the risk (OR= 0.33, 95% CI= 0.14-0.72). The - 308G/A polymorphism was not associated with risk for depression. Finally, the C857-G308-A238 haplotype was associated with a decreased risk of depression (OR= 0.35, 95% CI= 0.15-0.82). CONCLUSION Our results show for the first time an association between TNF-α -857C/T and -238G/A polymorphisms and prenatal depression in Mexican mestizo population.

Oxidative stress equilibrium during obstetric event in normal pregnancy

Abstract Objective: The aim of this study was to determine malondialdehyde (MDA) concentration as an oxidative stress marker and total antioxidant capacity (TAC) in pregnancy before and after perinatal event. Methods: This study was performed on 200 healthy full-term pregnant women admitted to pregnancy resolution in Maternal-Child Hospital of Durango, Mexico. Oxidative stress and TAC were assessed through detection of lipid peroxidation by quantitation of thiobarbituric acid-reactive substances (TBARS) and TAC through ferric reducing ability of the plasma (FRAP). Results: Our results showed increased levels of MDA after vaginal delivery (VD). TAC was also increased after obstetric event, but it did not differ between VD and caesarean section. Conclusions: We demonstrated that MDA concentrations are increased two hours after obstetric event, and this increase correlates with VD. The TAC was increased as a compensatory mechanism during obstetric event. Another important finding is that women receiving analgesia administration in VD, as well as dexamethasone administration in caesarean section, experienced a protector effect that decreased MDA levels.

H1/H2 MAPT haplotype and Parkinson’s Disease in Mexican mestizo population

Parkinsons 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.