ABSTRACT
The clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, there are ACE2 polymorphisms that could influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.
Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Polymorphism, Single Nucleotide/genetics , COVID-19/virology , Exome/genetics , Female , Humans , Male , Open Reading Frames/genetics , RNA, Untranslated/genetics , Regulatory Sequences, Ribonucleic Acid/genetics , South AmericaABSTRACT
IBD is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities: Crohn's disease and ulcerative colitis. Although Crohn's disease and ulcerative colitis have historically been studied together because they share common features (such as symptoms, structural damage and therapy), it is now clear that they represent two distinct pathophysiological entities. Both Crohn's disease and ulcerative colitis are associated with multiple pathogenic factors including environmental changes, an array of susceptibility gene variants, a qualitatively and quantitatively abnormal gut microbiota and a broadly dysregulated immune response. In spite of this realization and the identification of seemingly pertinent environmental, genetic, microbial and immune factors, a full understanding of IBD pathogenesis is still out of reach and, consequently, treatment is far from optimal. An important reason for this unsatisfactory situation is the currently limited comprehension of what are the truly relevant components of IBD immunopathogenesis. This article will comprehensively review current knowledge of the classic immune components and will expand the concept of IBD immunopathogenesis to include various cells, mediators and pathways that have not been traditionally associated with disease mechanisms, but that profoundly affect the overall intestinal inflammatory process.
Subject(s)
Colitis, Ulcerative/immunology , Crohn Disease/immunology , Adaptive Immunity/immunology , Adult , Alarmins/genetics , Alarmins/physiology , Causality , Child , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/genetics , Crohn Disease/diagnosis , Crohn Disease/epidemiology , Crohn Disease/genetics , Cultural Evolution , Gene Expression Regulation/genetics , Humans , Immunity, Innate/immunology , Inflammasomes/immunology , MicroRNAs/genetics , Microbiota/immunology , Regulatory Sequences, Ribonucleic Acid/geneticsABSTRACT
La estructura de la información presente en las regiones genéticas no codificadoras aún está muy poco caracterizada. En este trabajo se plantea como objetivo fundamental hacer una recodificación de estas secuencias y utilizar medidas teórico-informacionales de análisis, como la entropía de Shannon y la complejidad de Lempel-Ziv, para caracterizar estos datos. La complejidad de Lempel-Ziv mostró un patrón similar no aleatorio en secuencias no codificadoras de diferentes organismos; con medidas derivadas de la entropía de Shannon se obtuvieron evidencias de patrones que hacen posible un tipo de codificación diferente al código de tripletes clásico planteado para secuencias codificadoras(AU)