Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10-8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

Leisure-time physical activity and cardiometabolic risk among children and adolescents / Atividade física de lazer e risco cardiometabólico em crianças e adolescentes

OBJECTIVE: To assess the effect of Leisure-time physical activity (LTPA) on cardiometabolic risk by nutritional status in Mexican children and adolescents. METHODS: This was a cross-sectional study conducted with 1,309 participants aged between 5 and 17 years. Nutritional status was classified according to the BMI Z-score by age and gender. A previously validated questionnaire was used to evaluate LTPA; a cardiometabolic risk score was calculated. Multiple linear regression analysis was performed to assess the effect of LTPA on cardiometabolic risk. RESULTS: After adjusting for risk factors, mild LTPA were positively associated with cardiometabolic risk score (ßMildvsIntenseLTPA: 0.68; 95% CI: 0.18 to 1.18; pfortrend = 0.007). This association became stronger when estimated for overweight (ß MildvsIntenseLTPA: 1.24; 95% CI: 0.24 to 2.24; pfortrend = 0.015) and obese participants (ß MildvsIntenseLTPA: 1.02; 95% CI: 0.07 to 1.97; pfortrend= 0.045) CONCLUSION: Mild LTPA was positively associated with cardiometabolic risk in overweight and obese children and adolescents. Given the emerging childhood obesity epidemic in Mexico, these results may be useful in the design of strategies and programs to increase physical activity levels in order to achieve better health. .

OBJETIVO: Avaliar o efeito da prática de AFL sobre o risco cardiometabólico em crianças e adolescentes mexicanos de acordo com sua situação nutricional. MÉTODOS: Estudo transversal feito com 1.309 participantes de cinco a 17 anos. A situação nutricional foi classificada de acordo com o escore z de IMC por idade e sexo. Um questionário validado anteriormente foi usado para avaliar a AFL; foi calculado um escore de risco cardiometabólico. A análise de regressão linear múltipla foi feita para avaliar o efeito de AFL sobre o risco cardiometabólico. RESULTADOS: Após o ajuste de acordo com os fatores de risco, a AFL leve foi positivamente associada ao escore de risco cardiometabólico (ßAFLLevexIntensa: 0,68; IC 95%: 0,18 a 1,18; p paratendência = 0,007). Essa associação foi mais intensa quando estimada para participantes acima do peso (ßAFLLevexIntensa: 1,24; IC 95%: 0,24 a 2,24; p paratendência = 0,015) e obesos (ßAFLLevexIntensa: 1,02; IC 95%: 0,07 a 1,97; p paratendência = 0,045). CONCLUSÃO: A AFL leve foi positivamente associada ao escore de risco cardiometabólico em crianças e adolescentes acima do peso e obesos. Considerando a epidemia de obesidade infantil emergente no México, esses resultados poderão ser úteis na elaboração de estratégias e programas para aumentar os níveis de atividade física a fim de obter uma saúde melhor. .

La obesidad infantil como consecuencia de la interacción entre firmicutes y el consumo de alimentos con alto contenido energético / Childhood obesity is associated to the interaction between firmicutes and high energy food consumption

Introducción: La obesidad es un grave problema de salud pública en México, la Encuesta Nacional de Salud y Nutrición (ENSANUT 2012) reporta una prevalencia de sobrepeso y obesidad en niños de 5 a 11 años de 34.4%, siendo el país con mayor prevalencia a nivel mundial. Investigaciones recientes han sugerido que la microbiota intestinal puede ser factor de riesgo de la obesidad por su influencia en el metabolismo humano. Objetivo: Evaluar si existe asociación entre el perfil de la microbiota intestinal y la obesidad infantil y si esta asociación se modifica dependiendo del patrón de alimentación de una muestra de niños de edad escolar de la Ciudad de México. Metodología y Resultados: Estudio transversal en 1042 niños de 6 a 14 años, a todos se les aplicó cuestionario de actividad física, antecedentes patológicos personales y heredofamiliares de obesidad y diabetes tipo 2. La definición de los patrones de alimentación se realizó por análisis de componentes principales (ACP). La asociación entre microbiota intestinal y sobrepeso/obesidad dependiendo de la dieta se evaluó con modelos de regresión logística, ajustados por factores de confusión. Encontramos que un perfil de abundancia relativa alta de Firmicutes y una abundancia relativa baja de Bacteroidetes aunado a un consumo elevado de dietas ricas en carbohidratos y grasas saturadas se asocia con un mayor riesgo de obesidad. Conclusión: La interacción entre la microbiota intestinal y la dieta, particularmente con alto contenido de grasas y carbohidratos simples incrementa las posibilidades de presentar obesidad (AU)

Introductión: Obesity is a serious public health problem in Mexico, the National Health and Nutrition Survey (ENSANUT 2012) reported a 34.4% prevalence of overweight, and obesity in children aged 5-11. Recent research has suggested that the gut microbiota may be a risk factor of obesity through its influence on human metabolism. Aim of the study: To evaluate association between the intestinal microbiota profile and obesity among children and whether this association is modified depending on the feeding pattern of a sample of schoolchildren from Mexico City. Metodology and Results: Cross-sectional study on 1042 children aged 6-14 years; physical activity questionnaire, personal medical history and heredofamilial of obesity and type 2 diabetes were administered to all the children. Eating patterns was performed by principal component analysis (PCA). The association between intestinal microbiota and overweight / obesity depending on diet was assessed with logistic regression models. Conclusion: Our results shows that the interaction between the intestinal microbiota and diet, particularly high in fats and simple carbohydrates increases the chance of developing obesity (AU)

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)