Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer's development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.

Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

Association of B1 and B3 adrenergic receptors gene polymorphisms with insulin resistance and high lipid profiles related to type 2 diabetes and metabolic síndrome / Asociación de los polimorfismos génicos de los receptores adrenérgicos B1 y B3 con la resistencia a la insulina y los perfiles elevados de lípidos relacionados con la diabetes tipo 2 y el síndrome metabólico

Background: Among the diverse genes associated to type 2 diabetes (T2D), the β-adrenergic receptors are an excellent candidate to study in Mexican population. The objective of this work was to analyze the association of polymorphisms in ADRB1 (rs1801253) (Arg389Gly) and ADRB3 (Trp64Arg) genes with T2D and metabolic syndrome (MS). Methods: We studied 445 MS patients, 502 with T2D and 552 healthy controls. Anthropometric features and complete biochemical profile were evaluated, and Arg389Gly and Trp64Arg SNPs were determined by TaqMan assays. Data analysis was adjusted by African, Caucasian and Amerindian ancestral percentage. Results: The variant Arg389Gly of ADRB1 was statistically associated with an increase of LDL levels (P < 0.008), and the variant ADRB3 Trp64Arg was associated to larger HOMA-IR (P < 0.018) and with an increase of insulin levels (P < 0.001). A multiple logistic regression analysis was made in three grouping models: For ADRB3 in the codominant model Trp/Arg genotype, there was an OR of 1.53 (1.09-2.13, P < 0.003) which was increased up to OR 2.99 (1.44-6.22, P < 0.003) for the Arg/Arg genotype. Similar risk association was found under the dominant model Trp/Arg-Arg/Arg genotype with OR 1.67 (1.21-2.30; P < 0.002). In the recessive model (Arg/Arg genotype), there was also a high association OR 2.56 (1.24-5.26, P < 0.01). Conclusions: The ADRB3 Trp64Arg variant is a susceptibility gene polymorphism for T2D and the ADRB1 Gly389Arg for lipid metabolism disruption. These results show that these variants are potential biomarkers for predicting metabolic alterations and evolution in diabetic and metabolic syndrome patients (AU)

Antecedentes: Entre los diversos genes asociados a la diabetes tipo 2 (DT2), los receptores β -adrenérgicos- son excelentes candidatos para estudiar en la población mexicana dada la alta prevalencia de estas patologías. El objetivo de este trabajo fue analizar la asociación de polimorfismos en los genes ADRB1 (rs1801253) (Arg389Gly) y ADRB3 (Trp64Arg) con DT2 y SM. Métodos: Se estudiaron 445 pacientes con Síndrome Metabólico, 502 con diabetes tipo 2 y 552 controles sanos. Se evaluaron las características antropométricas, perfil bioquímico completo y los polimorfismos Arg389Gly y Trp64Arg SNPs se determinaron mediante ensayos TaqMan. El análisis de datos fue ajustado por porcentaje de ancestralidad. Resultados: Para la variante ADRB1 Arg389Gly se observó una asociación estadísticamente significativa con un aumento de los niveles de LDL (P < 0,008), y la variante ADRB3 Trp64Arg se asoció a mayor HOMA- IR (p < 0,018) y con un aumento de los niveles de insulina (P < 0,001). Mediante modelos de regresión logística múltiple en los tres modelos de heredabilidad se evaluó la asociación de ambos polimorfismos y DT2 y SM, observando un asociación significativa en los 3 modelos solo con DT2, ADRB3 en el modelo codominante Trp/Arg un OR de 1.53 (1.9 a 2.13 , P < 0.003) que se incrementó hasta OR 2,99 (1,44 a 6,22 , P < 0,003) para el genotipo Arg/Arg . Se encontró bajo el modelo dominante genotipo Trp/Arg- Arg/Arg con OR 1.67 (1.21 a 2.30, p < 0.002). En el modelo recesivo (Arg/Arg), también un OR 2.56 (1.24 a 5.26, P < 0.01). Conclusiones: La variante ADRB3 Trp64Arg se asoció significativamente con DT2 y ADRB1 Gly389Arg en alteraciones en el metabolismo de lípidos. Nuestros resultados demuestran que estas variantes son posibles biomarcadores para predecir las alteraciones metabólicas y la evolución en pacientes con síndrome Metabólico y diabetes tipo 2 (AU)