Impact and evolution of risk factors associated with hospitalization and mortality due to COVID-19 during the six epidemic waves in Mexico.

Objectives: This study aims to analyze and compare the main risk factors for hospitalization and deaths due to COVID-19 during the six epidemic waves from February 2020 to June 2023 in Mexico. Methods: First, a descriptive analysis of the risk factors that led to hospitalization and mortality due to COVID-19 was performed. Next, the degree of relationship of each risk factor with hospitalization and death was determined using Cramer's V coefficient. Finally, logistic regression models were applied to estimate the odds ratios of the most statistically significant risk factors for hospitalization and mortality. Results: A direct relationship between age and the possibility of hospitalization and death due to COVID-19 was found. Moreover, the comorbidities most likely to lead to hospitalization and death were pneumonia, hypertension, diabetes, obesity and CKD. It is also remarkable that the second factor of death is endotracheal intubation. Conclusion: The COVID-19 pandemic in Mexico revealed the reality of an epidemiological scenario where infectious diseases and chronic degenerative diseases coexist and interrelate.

Biochemical and genetic biomarkers associated with nicotine dependence in Mexican smokers.

Cigarette smoking remains an important health concern and is still a leading cause of preventable mortality. Nicotine is the substance responsible for sustained tobacco use and dependence. Identification of biomarkers underlying nicotine dependence behavior is important to identify people at risk for this dependence. In the present study, we identified biochemical and genetic biomarkers of nicotine dependence detected by the Fagerström Test for Nicotine Dependence (FTDN) in Mexican smokers. The nicotine metabolites nicotine-N'-oxide, trans-3'-hydroxycotinine-glucuronide (3HC-O-Gluc), and nicotine-N-Gluc (Gluc) were useful to differentiate nicotine-dependent from non-dependent subjects (p < .0001) with an area under the curve (AUC) of 0.7818. Genetic variants in CYP2A6, FMO3, and UGT2B7 (rs2431413, rs28363545, and rs7439326, respectively) were associated with nicotine dependence (p = .03, p = .01, p = .01, respectively). Variations in the enzymatic activity of CYP2A6 were associated with altered nicotine-N'-oxide and 3HC-O-Gluc levels. Decreased urinary levels of 3HC-O-Gluc and increased nicotine-N'-oxide were associated with a decrease in the functional activity of CYP2A6. A strong positive correlation was observed between the ratio of urinary 3HC/cotinine, a measure of CYP2A6 activity, and the levels of 3HC-O-Gluc (p < .0001, r = .6835), while a strong negative correlation was observed with nicotine-N'-oxide (p < .0001, r = .6522) in nicotine-dependent subjects. No correlations were observed in non-nicotine-dependent subjects. These data suggest that particular urinary nicotine metabolites and genetic variants involved in nicotine metabolism are useful to identify subjects with nicotine dependence in the Mexican population.

A Stochastic Phylogenetic Algorithm for Mitochondrial DNA Analysis.

This paper presents an exploratory analysis of the mitochondrial DNA (mtDNA) of 32 species in the subphylum Vertebrata, divided in 7 taxonomic classes. Multiple stochastic parameters, such as the Hurst and detrended fluctuation analysis (DFA) exponents, Shannon entropy, and Chargaff ratio are computed for each DNA sequence. The biological interpretation of these parameters leads to defining a triplet of novel indices. These new functions incorporate the long-range correlations, the probability of occurrence of nucleic bases, and the ratio of pyrimidines-to-purines. Results suggest that relevant regions in mtDNA can be located using the proposed indices. Furthermore, early results from clustering algorithms indicate that the indices introduced might be useful in phylogenetic studies.

Thymidylate synthase gene variants as predictors of clinical response and toxicity to fluoropyrimidine-based chemotherapy for colorectal cancer.

BACKGROUND: Fluoropyrimidines form the chemotherapy backbone of advanced and metastatic colorectal cancer (CRC). These drugs are frequently associated with toxicity events that result in dose adjustments and even suspension of the treatment. The thymidylate synthase (TYMS) gene is a potential marker of response and toxicity to fluoropyirimidines as this enzyme is the molecular target of these drugs. Our aim was to assess the association between variants of TYMS with response and toxicity to fluoropyrimidines in patients with CRC in independent retrospective and prospective studies. METHODS: Variants namely rs45445694, rs183205964, rs2853542 and rs151264360 of TYMS were genotyped in 105 CRC patients and were evaluated to define their association with clinical response and toxicity to fluoropyrimidines. Additionally, the relationship between genotypes and tumor gene expression was analyzed by quantitative polymerase chain reaction. RESULTS: The 2R/2R (rs45445694) was associated with clinical response (p=0.05, odds ratio (OR)=3.45) and severe toxicity (p=0.0014, OR=5.21, from pooled data). Expression analysis in tumor tissues suggested a correlation between the 2R/2R genotype and low TYMS expression. CONCLUSIONS: The allele 2R (rs45445694) predicts severe toxicity and objective response in advanced CRC patients. In addition, the alleles G(rs2853542) and 6bp-(rs151264360) are independent predictors of response failure to chemotherapy. This is the first study made on a Latin American population that points out TYMS gene variants have predictive values for response and toxicity in patients with CRC treated with fluoropyrimidine-based chemotherapy.

A New Gene Expression Signature for Triple Negative Breast Cancer Using Frozen Fresh Tissue before Neoadjuvant Chemotherapy.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer tumors. Comparisons between TNBC and non-triple negative breast cancer (nTNBC) may help to differentiate key components involved in TNBC neoplasms. The purpose of the study was to analyze the expression profile of TNBC versus nTNBC tumors in a homogeneous population from northeastern Mexico. A prospective study of 50 patients was conducted (25 TNBC and 25 nTNBC). Clinic parameters were equally distributed for TNBC and nTNBC: age at diagnosis (51 vs 47 years, p=0.1), glucose levels (107 mg/dl vs 104 mg/dl, p=0.64), and body mass index (28 vs 29, p=0.14), respectively. Core biopsies were collected for histopathological diagnosis and gene expression analyses. Total RNA was isolated and expression profiling was performed. 40 genes showed differential expression pattern in TNBC tumors. Among these, 9 over-expressed genes (PRKX/PRKY, UGT8, HMGA1, LPIN1, HAPLN3, and ANKRD11), and one under-expressed (ANX9) gene are involved in general metabolism. Based on this biochemical peculiarity, and the over-expression of BCL11A and FOXC1 (involved in tumor growth and metastasis, respectively) we validated by qPCR the expression profile of 7 genes out of the signature. In this report, a new gene signature for TNBC is proposed. To our knowledge, this is the first TNBC signature which describes genes involved in general metabolism. The findings may be pertinent for Mexican patients and require to be evaluated in further ethnic groups and populations.

CYP2D6 in Amerindians from Southern Mexico: low variability and higher frequency of functional alleles.

BACKGROUND: Several functional and nonfunctional CYP2D6 variants have been associated with interindividual and interethnic variability in pharmacological responses. The aim of this article was to study the diversity and the interpopulation relationships of CYP2D6 variants of south Native Mexicans to define predicted phenotypes. CONTENTS: A fully systematic review of CYP2D6 variants reported in Amerindian populations before 2015 was performed (NCBI, Google Scholar, and 1000 Genomes Project databases). Allele data were analyzed by methods such as heat map, dissimilarity matrix, dendogram, and principal component analysis using complete-linkage clustering method. Five original studies on CYP2D6 covering 13 Native Mexican populations were identified; three of these described CYP2D6 allele frequencies were in south Native Mexican populations. Overall, CYP2D6 allele variability is scarce in southern Native Mexican populations: besides the functional alleles *1 and *2 and the null variant *4, the other variants have frequencies <0.05. This implies that most of the southern Native Mexican populations may be considered CYP2D6 extended metabolizers. The statistical analyses tend to cluster the native communities by their geographical origin, but in a disperse pattern suggesting distinct subpopulation structures. CONCLUSIONS: CYP2D6 functional variants are prevalent in Native Mexicans, and they may be predicted as extended drug metabolizers. In addition, allele frequencies are related to the geographic distribution of the Amerindian groups and display important population stratification.

Interethnic relationships of CYP2D6 variants in native and Mestizo populations sharing the same ecosystem.

AIM: To analyze the distribution of CYP2D6 variants in two ethnically-related Mexican Native and Mestizo populations cohabitating the same econiche and their relationships with a distant Mestizo community. MATERIALS & METHODS: 314 volunteers were genotyped for CYP2D6 gene variants (*2, *3, *4, *6, *10, *13, *17, *35 and *41) using predesigned TaqMan probes. CYP2D6*5 and CYP2D6 wtxN were assessed by XL-PCR. RESULTS: CYP2D6*1, *2, *4 and *10 variants represented above 80.9% of total alleles. Chiapanecan communities showed low allele diversity compared with the northeastern population. Principal component analyses demonstrated clustering of both Mestizo populations. Variants associated to ultrarapid and poor metabolism were rare in Natives. CONCLUSION: Sharing of CYP2D6 alleles in both Chiapanecan populations suggests an ongoing gene-flow. Original submitted 8 December 2014; Revision submitted 13 February 2015.