Differential expression of PSMC4, SKP1, and HSPA8 in Parkinson's disease: insights from a Mexican mestizo population.

Parkinson's disease (PD) is a complex neurodegenerative condition characterized by alpha-synuclein aggregation and dysfunctional protein degradation pathways. This study investigates the differential gene expression of pivotal components (UBE2K, PSMC4, SKP1, and HSPA8) within these pathways in a Mexican-Mestizo PD population compared to healthy controls. We enrolled 87 PD patients and 87 controls, assessing their gene expression levels via RT-qPCR. Our results reveal a significant downregulation of PSMC4, SKP1, and HSPA8 in the PD group (p = 0.033, p = 0.003, and p = 0.002, respectively). Logistic regression analyses establish a strong association between PD and reduced expression of PSMC4, SKP1, and HSPA8 (OR = 0.640, 95% CI = 0.415-0.987; OR = 0.000, 95% CI = 0.000-0.075; OR = 0.550, 95% CI = 0.368-0.823, respectively). Conversely, UBE2K exhibited no significant association or expression difference between the groups. Furthermore, we develop a gene expression model based on HSPA8, PSMC4, and SKP1, demonstrating robust discrimination between healthy controls and PD patients. Notably, the model's diagnostic efficacy is particularly pronounced in early-stage PD. In conclusion, our study provides compelling evidence linking decreased gene expression of PSMC4, SKP1, and HSPA8 to PD in the Mexican-Mestizo population. Additionally, our gene expression model exhibits promise as a diagnostic tool, particularly for early-stage PD diagnosis.

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.

Lack of Association Between Cytomegalovirus Infection and Hypertensive Disorders in Pregnancy: A Case-Control Study in Durango, Mexico.

It is not clear whether infection with cytomegalovirus (CMV) is associated with hypertensive disorders in pregnant women. Through a case-control study design, 146 women suffering from hypertensive disorders in pregnancy (cases) and 146 age-matched normotensive pregnant women (controls) were examined for the presence of anti-CMV IgG and IgM antibodies with enzyme-linked immunoassays. IgM seropositive samples were further assayed by enzyme-linked fluorescent assay (ELFA). Anti-CMV IgG antibodies were found in 138 (94.5%) controls and in 136 (93.2%) cases (odds ratio [OR] = 0.78; 95% confidence interval [CI]: 0.30-2.05; P = 0.62). High (>18 IU/ml) levels of anti-CMV IgG antibodies were found in 37.7% of the 138 seropositive controls and in 34.6% of the 136 seropositive cases (OR = 0.87; 95% CI: 0.53-1.43; P = 0.59). Anti-CMV IgM antibodies were found in 1 (0.7%) of the controls but in none of the cases using ELFA (P = 1.0). Seropositivity to CMV was not associated with a previous preeclampsia and was similar among cases regardless their mean systolic and diastolic blood pressures, and mean arterial blood pressure. No serological evidence of an association between CMV infection and hypertensive disorders of pregnancy was found. Further research to elucidate the role of CMV in hypertensive disorders in pregnancy should be conducted.

Lack of Association between Mannose-binding Lectin 2 Codons 54 and 57 Gene Polymorphisms and Cervicovaginal Infections in Mexican Women.

The mannose-binding lectin (MBL) 2 gene has an important function in the innate immune response and activation of the third pathway of the complement system. Some studies have assessed the association of the MBL2 gene polymorphisms with cervicovaginal infections (CVI); however, there is no information about this association in Mexican women. This study aimed to determine the association between the MBL2 codons 54 and 57 gene polymorphisms with CVI in a sample of Mexican women. Through a cross-sectional study, blood samples and cervicovaginal cultures were obtain from 354 women. MBL2 genotyping was performed by real-time polymerase chain reaction with Taqman probes. Of the 354 women studied, 128 (36.2%) had CVI and 226 (63.8%) were healthy. The frequencies of the C and T variants in codon 54 in women with CVI were 83% and 17%, respectively; whereas the frequencies of these variants in healthy women were 82% and 18%, respectively. The frequencies of variants C/C, C/T, and T/T in women with CVI were 68%, 31%, and 1%, respectively; whereas the frequencies of these variants in healthy women were 68%, 29%, and 3%, respectively. With respect to codon 57, the frequencies of variants C and T were identical in women with CVI and in healthy women (97% and 3%, respectively). The frequencies of variants C/C, C/T, and T/T were identical in women with CVI and in healthy women (94%, 6%, and 0%, respectively). We conclude that MBL2 codons 54 and 57 gene polymorphisms do not associate with CVI in Mexican women.

Lack of Association Between Toxoplasma gondii Infection and Diabetes Mellitus: A Matched Case-Control Study in a Mexican Population.

BACKGROUND: Very little is known about the association between infection with Toxoplasma gondii (T. gondii) and diabetes mellitus. We perform an age- and gender-matched case-control study to determine the association of T. gondii infection and diabetes mellitus. METHODS: Cases included 156 patients with diabetes mellitus and 156 controls without diabetes mellitus who attended in two public clinics in Durango City, Mexico. Sera of cases and controls were tested for the presence of anti-Toxoplasma IgG and IgM antibodies using commercially available enzyme-linked fluorescence assays (ELFA). RESULTS: Anti-T. gondii IgG antibodies were found in 10 (6.4%) of the 156 cases and in five (3.2%) of the 156 controls (odds ratio (OR): 2.06; 95% confidence interval (CI): 0.69 - 6.19; P = 0.18). The frequency of high (> 150 IU/mL) anti-T. gondii IgG levels in seropositive cases (1/10: 10.0%) was comparable to the one (1/5: 20%) in seropositive controls (OR: 0.44; 95% CI: 0.02 - 9.03; P = 1.00). None of the 10 cases and five controls with seropositivity to anti-T. gondii IgG antibodies were positive for anti-T. gondii IgM antibodies. Stratification by gender showed similar frequencies of T. gondii infection in female cases (7/107: 6.5%) and female controls (4/107: 3.7%) (OR: 1.80; 95% CI: 0.51 - 6.34; P = 0.53), and in male cases (3/49: 6.1%) and male controls (1/49: 2.0%) (OR: 3.13; 95% CI: 0.31 - 31.19; P = 0.61). CONCLUSIONS: We conclude that there is not serological evidence of an association between T. gondii infection and diabetes mellitus in the studied subjects in Durango City, Mexico. Further studies to elucidate the role of T. gondii in diabetes should be conducted.

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

BACKGROUND: The 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. METHODS: Through 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. RESULTS: Seroprevalence 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). CONCLUSIONS: Our 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.

Haplotype analysis of TGF-ß1 gene in a preeclamptic population of northern Mexico.

OBJECTIVE: To determine the frequencies of -800G/A (rs1800468), -509C/T (rs1800469) and 869T/C (rs1800470) polymorphisms and their haplotypes in the TGF-ß1 gene and their association with preeclampsia in a population of northern México. DESIGN AND METHODS: This case-control study involved 175 preeclamptic and 253 normoevolutive pregnant women. The polymorphisms were genotyped by real time PCR. RESULTS: The allele and genotype frequencies of polymorphisms showed no significant differences between cases and controls; the -800AA genotype had a very low frequency in cases (1%) and controls (0.4%). The TT genotype of the 869T/C polymorphism is a protective factor of severe preeclampsia (OR 0.56, 95% CI 0.32-0.98). The -509C/T and 869T/C polymorphisms were in linkage disequilibrium (D'=.537, p=.009). The most common haplotypes in case and control groups were -800G/-509C/869C, 34.95% and 37.24%, respectively. We found no increased risk of preeclampsia by haplotype. CONCLUSIONS: Our results suggest that -800G/A, -509C/T and 869T/C polymorphisms of TGF-ß1 gene or their haplotypes are not associated with preeclampsia and that only the TT genotype of 869T/C polymorphism is a protective factor of severe preeclampsia in a population of northern México.

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.

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.