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Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.

Resumen: Objetivos: Describir la asociación entre las enfermedades crónicas no transmisibles y la edad, con la hospitalización, desenlaces clínicos graves y las defunciones por COVID-19 en los casos confirmados en población mexicana, comparando las tres primeras olas epidemiológicas de la pandemia en México. Diseño: Se realizó un análisis transversal utilizando el Sistema de Vigilancia Epidemiológica de Enfermedad Respiratoria Viral para COVID-19. Emplazamiento: Sistema de Vigilancia Epidemiológica de Enfermedad Respiratoria Viral en México (SISVER). Participantes: Población mexicana confirmada para SARS-CoV-2 registrada en el SISVER. Mediciones principales: Los desenlaces graves analizados fueron hospitalización, neumonía, necesidad de ventilación mecánica, ingreso a la UCI y defunción. Se evaluó la asociación (odds ratio [OR]) entre los desenlaces y las variables clínicas, comparando las tres olas epidemiológicas en México. Resultados: Una edad mayor de 65 años se asocia a un mayor porcentaje de hospitalización, neumonía, y notablemente, con el total de defunciones, independientemente del efecto de las comorbilidades crónicas. Existe interacción entre la edad en conjunto con la obesidad, la cual se asocia con la hospitalización y neumonía. Estos hallazgos fueron consistentes a lo largo de las tres olas epidemiológicas. Conclusión: La obesidad, EPOC y la diabetes en interacción con la edad se asocian con peores desenlaces clínicos, primordialmente con defunciones en los pacientes con COVID-19. Abstract: Objectives: To describe the association between chronic noncommunicable diseases and age with hospitalization, death and severe clinical outcomes for COVID-19 in confirmed cases within the mexican population, comparing the first three epidemiological waves of the pandemic in Mexico. Design: We performed an analysis using Mexico's Government Epidemiological Surveillance System database for COVID-19. Emplacement: Mexico's Epidemiological Surveillance System for Respiratory Diseases. Participants: Mexican population confirmed with SARS-CoV-2 registered on Mexico's Epidemiological Surveillance System for Respiratory Diseases. Primary measurements: The analysed severe outcomes were hospitalization, pneumonia, use of mechanical ventilation, intensive care unit admission and death. The association (odds ratio) between the outcomes and clinical variables was evaluated, comparing the three epidemiological waves in Mexico. Results: Age over 65 is associated with a higher ratio of hospitalization and pneumonia, independent of the effect of chronic comorbidities. There is an interaction between age and obesity, which is associated with hospitalization, pneumonia and highly associated with death. These findings were consistent throughout the three epidemiological waves. Conclusion: Obesity, COPD and diabetes in interaction with age, are associated with worse clinical outcomes and, more importantly, death in patients with COVID-19.

Objectives: The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated. Methods: A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components. Results: The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C. Conclusions: The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction.

Matrix metalloproteinases (MMP) are key players in the remodelling of the extracellular matrix under physiological and pathological conditions. Thermodynamic parameters of human recombinant metalloproteinases of the active (rMMP2, 3, 7, 8 and 9) and latent (rPro-MMP2, 3 and 9) forms were obtained by differential scanning calorimetry (DSC). Temperature by itself does not result in autocatalysis of recombinant MMP. The transitions observed by DSC correspond to structural domains of the monomeric protein. In this study, we show the domain organization of these proteins, where the thermal transition (Tm) of the main component is observed at 71.3 °C (ProMMP-2); 74.8 °C (ProMMP-8); 80.0 °C (ProMMP-3); 92.6 °C (ProMMP-9) and 98.3 °C (ProMMP-7). For MMP-3, this main Tm is related to the catalytic domain (CD). The isolated recombinant CD of MMP-3 unfolds as a single transition at Tm 83.4 °C, matching the more stable domain observed in the full-length active form of rMMP-3. The denaturation profile of rProMMP-3 shows the main transition at Tm 80 °C, a less stable domain before the propeptide domain (PD) cleavage. Our results indicate that the structural stability of MMP and particularly their CD are not substantially altered after cleavage of the PD. We propose that the thermodynamic parameters obtained by DSC are relevant for the functional study of MMP, particularly to reveal their contribution in complex biological samples in health and disease.