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.

Association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with metabolically healthy obesity.

BACKGROUND: Among the Toll-like receptors (TLR) that are dependent of myeloid response protein (MyD88), the TLR4 and TLR2 are directly associated with low-grade chronic inflammation; however, they are not been investigated in subjects with metabolically healthy obesity (MHO). Thus, the objective of this study was to determine the association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with MHO. METHODS AND RESULTS: Men and women with obesity aged 20 to 55 years were enrolled in a cross-sectional study. Individuals with MHO were allocated into the groups with and without low-grade chronic inflammation. Pregnancy, smoking, alcohol consumption, intense physical activity or sexual intercourse in the previous 72 h, diabetes, high blood pressure, cancer, thyroid disease, acute or chronic infections, renal impairment, and hepatic diseases, were exclusion criteria. The MHO phenotype was defined by a body mass index (BMI ≥ 30 kg/m2) plus one or none of the following cardiovascular risk factors: hyperglycemia, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol. A total of 64 individuals with MHO were enrolled and allocated into the groups with (n = 37) and without (n = 27) inflammation. The multiple logistic regression analysis indicated that TLR2 expression is significantly associated with inflammation in individuals with MHO. In the subsequent analysis adjusted by BMI, TLR2 expression remained associated with inflammation in individuals with MHO. CONCLUSION: Our results suggest that overexpression of TLR2, but not TLR4 and MyD88, is associated with low-grade chronic inflammation in subjects with MHO.

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.

Leptospira infection in people in the city of Durango, Mexico: a cross sectional study.

OBJECTIVE: To determine the seroprevalence of Leptospira immunoglobulin (Ig)G and IgM antibodies and its association with the characteristics of the study population from the northern Mexican city of Durango, Mexico. METHODS: Through a cross-sectional study design, inhabitants of Durango City, Mexico were surveyed between June 2018 and November 2018. Serum samples from the subjects were analysed for anti-Leptospira IgG and IgM antibodies using commercially available enzyme-linked immunosorbent assays. Sociodemographic, clinical, behavioural and housing characteristics were recorded. Data were analysed by bivariate and multivariate analyses. RESULTS: The study enrolled 413 people, of which 124 (30.0%) and 137 (33.2%) were positive for anti-Leptospira IgG antibodies and anti-Leptospira IgM antibodies, respectively. Multivariate analysis showed that Leptospira seropositivity was associated with professional occupation, alcohol consumption, ill clinical status, memory impairment and a history of surgery. CONCLUSIONS: This is the first study to report the seroepidemiology of Leptospira infection in an urban general population in the north of Mexico. The seroprevalence of Leptospira infection found was higher than those previously reported in Mexican studies.

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.

Toxoplasma gondii infection and multiple sclerosis: An age- and a gender-matched case-control seroprevalence study.

The link between Toxoplasma gondii infection and multiple sclerosis remains controversial. In the present study, we aimed to determine the association between T. gondii seropositivity and multiple sclerosis. Using an age- and gender-matched case-control study, we studied 45 patients who had multiple sclerosis attended in two public hospitals and 225 control subjects without this disease and other neurological disorders in Durango City, Mexico. Serum samples of cases and controls were analyzed for detection of anti-Toxoplasma IgG using a commercially available enzyme-linked immunoassay. One (2.22%) of the 45 patients with multiple sclerosis, and 15 (6.67%) of the 225 control subjects without this disease were seropositive for anti-T. gondii IgG antibodies. No statistically significant difference (OR = 0.31; 95% CI: 0.04-2.47; P = 0.48) in seroprevalence of anti-T. gondii IgG antibodies between cases and controls was found. The frequency of T. gondii seropositivity did not vary among cases and controls about sex or age groups. Results of this study do not support an association between seropositivity to T. gondii and multiple sclerosis. However, additional research with larger sample sizes to confirm this lack of association should be conducted.

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.

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.

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.

Toxoplasma gondii exposure and Parkinson's disease: a case-control study.

OBJECTIVES: To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. DESIGN: Case-control study. SETTING: Cases and controls were enrolled in Durango City, Mexico. PARTICIPANTS: 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. PRIMARY AND SECONDARY OUTCOME MEASURES: Serum samples of participants were analysed for anti-T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. RESULTS: Anti-T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti-T. gondii IgG positive cases and four of the anti-T. gondii IgG positive controls had anti-T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. CONCLUSIONS: The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted.

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).

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.

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.

Role of the novel protein TmcR in regulating the expression of the cel9-cel48 operon from Myxobacter sp. AL-1.

Northern-blot analysis revealed that cel9 and cel48, which encode family 9 and 48 glycosyl hydrolases, respectively, were expressed as a bicistronic mRNA in the soil bacterium Myxobacter sp. AL-1. The two cistrons of the cel9-cel48 mRNA as well as their encoded products were detected in stationary phase cultures of Myxobacter sp. AL-1, suggesting that a mechanism delayed the transcription of cel9-cel48 until this growth phase. Interestingly, in the same strand and orientation as cel48 a different reading frame was found fully embedded within another ORF encoding a novel DNA-binding protein termed TmcR (Temporal cellulase regulator). Results of Western-blot analysis revealed that although TmcR occurred in growing cells, its concentration decreased during the late stationary growth phase. A possible regulatory role of TmcR during cel9-cel48 expression was studied in E. coli. Results showed that in comparison with E. coli cells expressing cel9-cel48 cloned in pBR322, deletion of tmcR from this plasmid increased not only the cellulase activity but also the amount of Cel9 secreted to the culture medium. Moreover, both, the cellulase activity and Cel9 production decreased in E. coli cells when tmcR was cloned back in the plasmid lacking tmcR. These results suggest that TmcR has the properties required to repress the expression of the cel9-cel48 cluster from Myxobacter sp. AL-1 and suggest the existence of a mechanism involved in regulating the expression of cellulase genes in soil bacteria.