RESUMEN

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution and inference of identity-by-descent segments, we inferred ancestral population sizes across Mesoamerican regions over time, unravelling Indigenous, colonial and postcolonial demographic dynamics2-6. We observed variation in runs of homozygosity among genomic regions with different ancestries reflecting distinct demographic histories and, in turn, different distributions of rare deleterious variants. We conducted genome-wide association studies (GWAS) for 22 complex traits and found that several traits are better predicted using the Mexican Biobank GWAS compared to the UK Biobank GWAS7,8. We identified genetic and environmental factors associating with trait variation, such as the length of the genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into the genetic histories of individuals in Mexico and dissects their complex trait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.

Asunto(s)

Bancos de Muestras Biológicas , Genética Médica , Genoma Humano , Genómica , Hispánicos o Latinos , Humanos , Glucemia/genética , Glucemia/metabolismo , Estatura/genética , Índice de Masa Corporal , Interacción Gen-Ambiente , Marcadores Genéticos/genética , Estudio de Asociación del Genoma Completo , Hispánicos o Latinos/clasificación , Hispánicos o Latinos/genética , Homocigoto , México , Fenotipo , Triglicéridos/sangre , Triglicéridos/genética , Reino Unido , Genoma Humano/genética

RESUMEN

We previously observed beneficial effects of native banana starch (NBS) with a high resistant starch (RS) content on glycemic response in lean and obese participants. Here, we aimed to determine the effects of NBS and high-amylose maize starch (HMS) on glycemic control (GC) and glycemic variability (GV) in patients with type 2 diabetes (T2D) when treatments were matched for digestible starch content. In a randomized, crossover study, continuous glucose monitoring (CGM) was performed in 17 participants (aged 28-65 years, BMI ≥ 25 kg/m2, both genders) consuming HMS, NBS, or digestible maize starch (DMS) for 4 days. HMS and NBS induced an increase in 24 h mean blood glucose during days 2 to 4 (p < 0.05). CONGA, GRADE, and J-index values were higher in HMS compared with DMS only at day 4 (p < 0.05). Yet, NBS intake provoked a reduction in fasting glycemia changes from baseline compared with DMS (p = 0.0074). In conclusion, under the experimental conditions, RS from two sources did not improve GC or GV. Future longer studies are needed to determine whether these findings were affected by a different baseline microbiota or other environmental factors.

Asunto(s)

Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/complicaciones , Control Glucémico/métodos , Almidón Resistente/farmacología , Adulto , Amilosa , Automonitorización de la Glucosa Sanguínea , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad , Almidón/administración & dosificación , Zea mays/química

RESUMEN

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.

RESUMEN

Several studies have reported the role of hedgehog interacting protein-like 1 (HHIPL-1) in different pathologies, including cardiovascular disease. The aim of the present study was to analyze the association of HHIPL-1 (rs2895811) polymorphism with myocardial infarction (MI), cardiometabolic parameters, and traditional cardiovascular risk factors in the Mexican population. The polymorphism was genotyped using a TaqMan assay in 1023 patients with MI and 1105 controls. A similar distribution of the polymorphism was observed between studied groups. However, in patients group, the C allele was associated with a decreased risk of developing hypertriglyceridemia (OR = 0.757, Padditive = 0.030, OR = 0.685, Pdominant = 0.020, OR = 0.691, Pcodominant1 = 0.030), metabolic syndrome (OR = 0.746, Padditive = 0.030, OR = 0.647, Pdominant = 0.005, OR = 0.670, Pheterozygote = 0.015, OR = 0.637, Pcodominant1 = 0.005), and insulin resistance (OR = 0.681, Pdominant = 0.045). The results suggest that HHIPL-1 rs2895811 polymorphism is associated with cardiometabolic parameters in Mexican patients with MI.

Asunto(s)

Hipertrigliceridemia/genética , Resistencia a la Insulina/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Síndrome Metabólico/genética , Infarto del Miocardio/genética , Polimorfismo de Nucleótido Simple , Adulto , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , México , Persona de Mediana Edad , Factores de Riesgo

RESUMEN

OBJECTIVES: Spondyloarthritis (SpA) is often diagnosed late in the course of the disease and improved methods for early diagnosis are required. We have tested the ability of genetic profiling to diagnose axial SpA (axSpA) as a whole group, or ankylosing spondylitis (AS) alone, in a cohort of chronic back pain patients. METHODS: 282 patients were recruited from centres in the United Kingdom, Germany, Taiwan, Canada, Columbia and Turkey as part of the ASAS classification criteria for axSpA study (ASAS cohort). Subjects were classified according to the ASAS axSpA criteria, and the modified New York Criteria for AS. Patients were genotyped for ~200,000 immune-mediated disease SNPs using the Illumina Immunochip. RESULTS: We first established the predictive accuracy of genetic data comparing 9,638 healthy controls and 4,428 AS cases from the homogenous International Genetics of AS (IGAS) Consortium Immunochip study which showed excellent predictive power (AUC=0.91). Genetic risk scores had lower predictive power (AUC=0.83) comparing ASAS cohort axSpA cases meeting the ASAS imaging criteria with IGAS controls. Comparing genetic risk scores showed moderate discriminatory capacity between IGAS AS and ASAS imaging positive cases (AUC 0.67±0.05), indicating that significant differences in genetic makeup exist between the cohorts. CONCLUSIONS: In a clinical setting of referred back pain patients suspected to have axial SpA we were unable to use genetic data to construct a predictive model better than that based on existing clinical data. Potential confounding factors include significant heterogeneity in the ASAS cohort, possibly reflecting the disease heterogeneity of axSpA, or differences between centres in ascertainment or classification performance.

Asunto(s)

Dolor de Espalda/diagnóstico , Dolor de Espalda/genética , Dolor Crónico/diagnóstico , Dolor Crónico/genética , Perfilación de la Expresión Génica/métodos , Pruebas Genéticas/métodos , Articulaciones/fisiopatología , Polimorfismo de Nucleótido Simple , Columna Vertebral/fisiopatología , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/genética , Adulto , Área Bajo la Curva , Dolor de Espalda/etnología , Dolor de Espalda/fisiopatología , Canadá , Estudios de Casos y Controles , Dolor Crónico/etnología , Dolor Crónico/fisiopatología , Colombia , Diagnóstico Precoz , Europa (Continente) , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Valor Predictivo de las Pruebas , Curva ROC , Factores de Riesgo , Espondilitis Anquilosante/etnología , Espondilitis Anquilosante/fisiopatología , Taiwán , Adulto Joven

RESUMEN

El acople de un ligando con un receptor induce una señal que viaja a través de este último hasta llegar a su dominio intracelular, donde desencadena una cascada de respuesta. Analizando el acople del Receptor de Células T (TCR) con antígenos foráneos, los autores identificaron patrones moleculares de geometría planar al interior de este receptor, capaces de internalizar la señal producida por el acople TCR/Antígeno. Este mecanismo fue también hallado en diversidad de sistemas receptor-ligando de diferente funcionalidad biológica, tales como las parejas Bomba de Calcio-ADP, el acople viral gp120-CD4 y el sistema Hemoglobina-Oxígeno. Dicho mecanismo identificado por los autores es de naturaleza Cuántica y permitiría explicar la transducción de señales en todo tipo de receptores bioquímicos. Este hallazgo facilitaría el diseño de péptidos-vacuna con alta capacidad inmunogénica así como el desarrollo de nuevos medicamentos.

---

The coupling of a ligand with a receptor induces a signal that travels through the receptor until it reaches the intracellular domain, where it triggers a response cascade. By analyzing the coupling of receptor cells (TCR) with foreign antigens, the authors identified the presence of molecular patterns, planar in geometry, within this receptor, that are capable of internalizing the signal produced by TCR/antigen coupling. This mechanism, also found in a range of receptor-ligand systems with greatly differing biological functions, including calcium pump-ADP, gp120-CD4 viral coupling, and the hemoglobin-oxygen system, is quantum in nature and capable of explaining the means of signal transduction in all kinds of biochemical receptors. As such, the finding may facilitate the design of vaccine-peptides with high immunogenicity, as well as make it possible to develop new drugs.

---

O acoplamento de um ligante com um receptor induz um sinal que viaja através do receptor atingindo seu domínio intracelular onde desencadeia uma cascata de resposta. Analisando o acoplamento do Receptor de Células T (TCR) com antígenos forâneos, os autores identificaram padrões moleculares de geometria planar no interior desse receptor, capazes de internalizar o sinal produzido pelo acoplamento TCR/ Antígeno. Esse mecanismo também foi encontrado em múltiplos sistemas receptor-ligante de diferente funcionalidade biológica, tais como os pares Bomba de Cálcio-ADP, o acoplamento viral gp120-CD4 e o sistema de Hemoglobina-Oxigênio. Tal mecanismo identificado pelos autores é de natureza Quântica e permitiria explicar a transdução de sinais em todo tipo de receptores bioquímicos. Este achado também facilitaria o desenho de peptídeos-vacina com alta capacidade imunogênica bem como o desenvolvimento de novos medicamentos.

Asunto(s)

Campos Electromagnéticos , Receptores de Antígenos de Linfocitos T , Transducción de Señal , Hemoglobinas , Oxígeno

RESUMEN

Single-nucleotide polymorphisms (SNPs) in the protein phosphatase and actin regulator 1 gene (PHACTR1) have been associated with susceptibility to develop several diseases, including cardiovascular disease. The purpose of this study was to evaluate the role of two polymorphisms (rs2026458 and rs9349379) of the PHACTR1 gene in the susceptibility to the risk of developing premature coronary artery disease (CAD) in the Mexican population. The genotype analysis was performed using 5'exonuclease TaqMan genotyping assays in a group of 994 patients with premature CAD and 703 controls. A similar genotype distribution of rs2026458 was observed in both groups; however, under an additive model adjusted by age, body mass index, type 2 diabetes mellitus, smoking, dyslipidemia, and hypertension, the rs9349379 G allele was associated with a higher risk for developing premature CAD (odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.03-1.46, p-value (p) = 0.024). The two PHACTR1 polymorphisms were not in linkage disequilibrium. In summary, our results suggest that the PHACTR1 rs9349379 polymorphism plays an important role in the risk of developing premature CAD in the Mexican population.

Asunto(s)

Enfermedad de la Arteria Coronaria/genética , Predisposición Genética a la Enfermedad/genética , Proteínas de Microfilamentos/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Alelos , Enfermedad de la Arteria Coronaria/epidemiología , Dislipidemias/genética , Femenino , Genotipo , Humanos , Hipertensión/genética , Masculino , México , Persona de Mediana Edad , Oportunidad Relativa

RESUMEN

A partir del reciente hallazgo de campos electromagnéticos planares en sistemas proteicos, se propone un mecanismo para explicar la seleccion, atraccion y acople de peptidos con las moleculas de HLA-II para su posterior presentacion a celulas T-Helper. El mecanismo aqui planteado explica dichos acoples por primera vez sin recurrir al paradigma de acople molecular "Llave-Cerrojo". Aplicando estos patrones electromagneticos, se disenaron ocho peptidos con mejor capacidad acoplante con la molecula de HLA-II que el peptido de acople universal conocido como CLIP, lo cual indica que esta metodologia facilita el diseno de peptidos-vacuna con altos valores de binding. Estos patrones electromagneticos descubiertos por los autores permitieron tambien explicar la capacidad de acople universal del peptido CLIP, asi como proporcionar multiples soluciones a problemas de la Bioquimica y la Inmunologia Molecular que seran expuestos en trabajos posteriores.(AU)

---

Following the recent discovery of planar electromagnetic fields in protein systems, this work proposes a mechanism to explain the action of HLA-II molecules in selecting, attracting and coupling with peptide-antigens prior to their presentation to T-helper cells. The mechanism explains such couplings for the first time without recourse to the molecular "key-lock" paradigm. Using these electromagnetic field patterns, eight peptides were designed that showed better coupling capacity with HLA-II molecules than the native CLIP peptide. The novel methodology enables the design of vaccinepeptides with high binding capacity. The discovered electromagnetic patterns further offer an explanation of the universal coupling capacity of CLIP and give rise to a number of solutions and new concepts in molecular immunology.(AU)

---

Desde a descoberta recente de campos eletromagnéticos plano em sistemas proteicos, os autores prop§em um mecanismo para explicar a seleþÒo, a atraþÒo e o acoplamento de peptídeos com moléculas HLA-II para subsequente apresentaþÒo de células T-Helper. O mecanismo criado explica tais acoplamentos pela primeira vez, sem recorrer ao paradigma de acoplamento molecular "Key-Lock". Aplicando estes padr§es eletromagnéticos, foram criados oito peptídeos com melhor acoplamento com a molécula HLA-II do que o peptídeo de anexar universal conhecido como CLIP, que indica que esta metodologia facilita o projeto de peptídeos-vacuna com altos valores de ligaþÒo. Estes padr§es eletromagnéticos descobertos pelos autores permitiram também explicar a capacidade do CLIP de peptídeo de acoplamento universal, bem como fornecem múltiplas soluþ§es para problemas de Bioquímica e Imunologia Molecular, que será exibido em trabalhos posteriores.(AU)

RESUMEN

A partir del reciente hallazgo de campos electromagnéticos planares en sistemas proteicos, se propone un mecanismo para explicar la selección,atracción y acople de péptidos con las moléculas de HLA-II para su posterior presentación a células T-Helper. El mecanismo aquí planteado explica dichos acoples por primera vez sin recurrir al paradigma de acople molecular “Llave-Cerrojo”. Aplicando estos patrones electromagnéticos, se diseñaron ocho péptidos con mejor capacidad acoplante con la molécula de HLA-II que el péptido de acople universal conocido como CLIP, lo cual indica que esta metodología facilita el diseño de péptidos-vacuna con altos valores de binding. Estos patrones electromagnéticos descubiertos por los autores permitieron también explicar la capacidad de acople universal del péptido CLIP, así como proporcionar múltiples soluciones a problemas de la Bioquímica y la Inmunología Molecular que serán expuestos en trabajos posteriores...

Asunto(s)

Humanos , Complejo Antígeno-Anticuerpo , Antígenos , Biosíntesis de Péptidos , Campos Electromagnéticos , Vacunas

RESUMEN

There are limited and conflicting data from clinical trials concerning the beneficial effects of magnesium supplementation on diabetic patients. We investigated the effects of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia. A total of 98 normomagnesemic subjects with type 2 diabetes were enrolled in a randomized, crossover, double-blind, placebo-controlled trial. Participants were randomly assigned to receive magnesium lactate (360 mg elemental magnesium) or placebo for three months, followed by a three-month washout period. Treatment assignments were then reversed over an additional three months of follow-up. The primary endpoint was a reduction in fasting glucose and HbA1c. A total of 56 subjects completed the follow-up in the magnesium and placebo supplementation groups. Urinary magnesium excretion was increased following magnesium supplementation in the intervention group compared with the placebo group (p = 0.0002). Fasting glucose, HbA1c, insulin and HOMA-IR, as well as lipid profile, did not change significantly during treatment. We concluded that magnesium supplementation does not improve metabolic control or insulin sensitivity in diabetic subjects with normomagnesemia.

Asunto(s)

Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos , Resistencia a la Insulina/fisiología , Magnesio/administración & dosificación , Magnesio/sangre , Adulto , Anciano , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento

RESUMEN

Partiendo del alineamiento múltiple de secuencias proteicas humanas obtenidas de las bases de datos del National Center of Biotechnology Information (NCBI) y su posterior análisis espacial tridimensional, se estableció la existencia de un patrón de acople universal para péptidos presentados por las moléculas de histocompatibilidad HLA-II (DR, DP y DQ), siendo una base para el diseño de vacunas proteicas. Estos patrones espaciales fueron claramente exhibidos por los residuos altamente conservados de los tres tipos de moléculas de HLA-II. La aplicación de este nuevo hallazgo permitió diseñar péptidos con mejores valores de acople péptido-HLA-II, que los generados por el péptido de acople universal conocido como CLIP (class Il-associated invariant chain peptide).

---

Starting from the multiple alignment of human protein sequences obtained from the NCBI database (National Center of Biotechnology Information) and subsequent three-dimensional spatial analysis, the existence of a pattern of universal coupling to peptides presented by MHC molecules HLA-II (DR, DP and DQ) was established, being a basis for the design of protein vaccines. These spatial patterns were clearly exhibited by highly conserved residues of the three kinds of HLA-II molecules. The application of this new finding made it possible to design peptides with better Peptide -HLA-II coupling values than those generated by the universal coupling peptide called CLIP (class II-associated invariant chain peptide).

---

FA partir do alinhamento múltiplo de sequéncias de proteínas humanas obtidas a partir das bases de dados do NCBI (National Center of Biotechnology Information) e análise espacial tridimensional subsequente, estabeleceu-se a existéncia de um padráo de acoplamento universal para peptídeos apresentados pelas moléculas de histocompatibilidade HLA-II (DR, DP e DQ), sendo uma base para o desenho de vacinas proteicas. Estes padroes espaciais foram claramente exibidos pelos residuos altamente conservados dos trés tipos de moléculas de HLA-II. A aplicagáo deste novo achado permitiu desenhar peptídeos com melhores valores de acoplamento peptídeo-HLA-II, do que aqueles gerados pelo peptídeo de acoplamento universal conhecido como CLIP (classe II-peptídeo associado a cadeia invariante).

Asunto(s)

Humanos , Histocompatibilidad , Antígenos HLA , Complejo Mayor de Histocompatibilidad , Sondas de ADN de HLA , Antígenos de Histocompatibilidad , Antígenos de Histocompatibilidad Clase II , Vacunas

RESUMEN

Partiendo del alineamiento múltiple de secuencias proteicas humanas obtenidas de las bases de datos del National Center of Biotechnology Information (NCBI) y su posterior análisis espacial tridimensional, se estableció la existencia de un patrón de acople universal para péptidos presentados por las moléculas de histocompatibilidad HLA-II (DR, DP y DQ), siendo una base para el diseño de vacunas proteicas. Estos patrones espaciales fueron claramente exhibidos por los residuos altamente conservados de los tres tipos de moléculas de HLA-II. La aplicación de este nuevo hallazgo permitió diseñar péptidos con mejores valores de acople péptido-HLA-II, que los generados por el péptido de acople universal conocido como CLIP (class Il-associated invariant chain peptide).(AU)

---

Starting from the multiple alignment of human protein sequences obtained from the NCBI database (National Center of Biotechnology Information) and subsequent three-dimensional spatial analysis, the existence of a pattern of universal coupling to peptides presented by MHC molecules HLA-II (DR, DP and DQ) was established, being a basis for the design of protein vaccines. These spatial patterns were clearly exhibited by highly conserved residues of the three kinds of HLA-II molecules. The application of this new finding made it possible to design peptides with better Peptide -HLA-II coupling values than those generated by the universal coupling peptide called CLIP (class II-associated invariant chain peptide).(AU)

---

FA partir do alinhamento múltiplo de sequéncias de proteínas humanas obtidas a partir das bases de dados do NCBI (National Center of Biotechnology Information) e análise espacial tridimensional subsequente, estabeleceu-se a existéncia de um padráo de acoplamento universal para peptídeos apresentados pelas moléculas de histocompatibilidade HLA-II (DR, DP e DQ), sendo uma base para o desenho de vacinas proteicas. Estes padroes espaciais foram claramente exibidos pelos residuos altamente conservados dos trés tipos de moléculas de HLA-II. A aplicagáo deste novo achado permitiu desenhar peptídeos com melhores valores de acoplamento peptídeo-HLA-II, do que aqueles gerados pelo peptídeo de acoplamento universal conhecido como CLIP (classe II-peptídeo associado a cadeia invariante).(AU)