High relative abundance of firmicutes and increased TNF-α levels correlate with obesity in children.

OBJECTIVE: To investigate the correlation among pro- or anti-inflammatory cytokines and the two main gut microbiota phyla in obese children. MATERIALS AND METHODS: Anthropometric data were obtained from 890 children under 14 years old to determine the degree of obesity. Serum cytokine concentration was measured by ELISA. Relative abundance of gut microbiota in feces was evaluated by quantitative RealTime PCR assays. RESULTS: Anthropometric and biochemical parameters were statistically higher in overweigth/ obese children (OW/O) than in lean (NW), Increased TNF-α levels were found in obese children that also have a high relative abundance of Firmicutes. CONCLUSIONS: Obese children have a high relative abundance of Firmicutes that correlates with increased levels of TNF-α. This is the first study that shows a relation between Firmicute abundance and TNF-α serum concentration in obese children.

High relative abundance of firmicutes and increased TNF-α levels correlate with obesity in children / Obesidad infantil y su correlación con la alta abundancia relativa de firmicutes y el aumento de los niveles de TNF-α

Abstract: Objective: To investigate the correlation among pro- or anti-inflammatory cytokines and the two main gut microbiota phyla in obese children. Materials and methods: Anthropometric data were obtained from 890 children under 14 years old to determine the degree of obesity. Serum cytokine concentration was measured by ELISA. Relative abundance of gut microbiota in feces was evaluated by quantitative Real-Time PCR assays. Results: Anthropometric and biochemical parameters were statistically higher in overweight /obese children than in lean ones. Increased TNF-α levels were found in obese children that also have a high relative abundance of Firmicutes. Conclusions: Obese children have a high relative abundance of Firmicutes that correlates with increased levels of TNF-α. This is the first study that shows a relation between Firmicute abundance and TNF-α serum concentration in obese children.

Resumen: Objetivo: Investigar la correlación entre las citocinas proinflamatorias o antiinflamatorias y los dos principales filos de la microbiota intestinal en niños obesos. Material y métodos: Se obtuvieron mediciones antropométricas de 890 niños de 6 a 14 años; posteriormente se clasificaron en normopeso y sobrepeso/obeso. Las concentraciones séricas fueron medidas por el método de ELISA. La abundancia relativa de la microbiota intestinal en heces se evaluó por PCR tiempo real. Resultados: Los parámetros bioquímicos y antropométricos fueron estadísticamente más altos en niños con sobrepeso / obesidad que en niños delgados. Se encontraron niveles más altos de FNT-α en niños obesos que también tenían una abundancia relativa alta de Firmicutes. Conclusiones: Los niños obesos tienen una alta abundancia relativa de Firmicutes, la cual se correlaciona con un incremento de los niveles de FNT-α. Este es el primer estudio que evalúa la reacción entre la abundancia de Firmicutes y la concentración sérica de FNT-α en niños obesos.

Copy Number Variations in Candidate Genes and Intergenic Regions Affect Body Mass Index and Abdominal Obesity in Mexican Children.

Introduction. Increase in body weight is a gradual process that usually begins in childhood and in adolescence as a result of multiple interactions among environmental and genetic factors. This study aimed to analyze the relationship between copy number variants (CNVs) in five genes and four intergenic regions with obesity in Mexican children. Methods. We studied 1423 children aged 6-12 years. Anthropometric measurements and blood levels of biochemical parameters were obtained. Identification of CNVs was performed by real-time PCR. The effect of CNVs on obesity or body composition was assessed using regression models adjusted for age, gender, and family history of obesity. Results. Gains in copy numbers of LEPR and NEGR1 were associated with decreased body mass index (BMI), waist circumference (WC), and risk of abdominal obesity, whereas gain in ARHGEF4 and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d and losses in INS were associated with increased BMI and WC. Conclusion. Our results indicate a possible contribution of CNVs in LEPR, NEGR1, ARHGEF4, and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d to the development of obesity, particularly abdominal obesity in Mexican children.

Elevated Levels of LDL-C are Associated With ApoE4 but Not With the rs688 Polymorphism in the LDLR Gene.

INTRODUCTION: Apolipoprotein E (ApoE) 4 isoform has been associated with elevated levels of cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs), meanwhile several polymorphisms in the LDL receptor (LDLR) gene have been associated with increased levels of total cholesterol and LDL-C. MATERIAL AND METHODS: We studied 400 women from Southwest Mexico. Anthropometric features and biochemical profile were evaluated, and genotyping of single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene and rs688 in the LDLR gene was determined by TaqMan assays. RESULTS: We found significant association between LDL-C (odds ratio [OR] = 3.3, 95% confidence interval [CI]: 1.9-5.7) and marginal association with TG (OR = 1.7, 95% CI: 1.0-2.9) of atherogenic risk in women carriers of the ApoE4 isoform compared to ApoE3. The TT genotype of rs688 in the LDLR gene was not found to be associated with elevated levels of total cholesterol or LDL-C. CONCLUSION: Our results show that carrier women of the ApoE4 isoform are more likely to have elevated levels of LDL-C and therefore increased risk of developing atherosclerosis.

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico.

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

[Copy number variation: markers and predictors for type 2 diabetes]. / Variaciones de número de copias: marcadores y predictores de diabetes tipo 2.

Type 2 diabetes (T2D) is a disease characterized by a deficiency in production or action of insulin. It is the result mainly of the interaction of the environment, lifestyle, as well as genetic factors. It is considered as one of the major health issues in the world because it affects severely the psychological well-being and overall life quality. Recently it has been shown that DNA copy number variations (CNVs) are associated with several diseases, including obesity and T2D. The CNVs are present from 9 to 18 % of the genome and can modify the expression levels of mRNA and proteins encoded by genes located near their localization. Less is known about their contribution to the pathogenesis of metabolic diseases, which is necessary to characterize so that these variations can be potentially used as biomarkers of genetic risk CNVs of T2D.

La diabetes tipo 2 (DT2) es una enfermedad caracterizada por una deficiencia en la producción o acción de la insulina; es el resultado de la interacción principalmente de factores ambientales, el estilo de vida, asícomo factores genéticos. Se considera como uno de los problemas de salud más importantes en el mundo debido a que afecta seriamente la independencia, el bienestar psicológico y en general la calidad de vida. Recientemente se ha demostrado que las variaciones en el número de copias de ADN (CNV, del inglés copy number variations) se asocian con diferentes enfermedades, entre ellas la obesidad y DT2. Las CNV se presentan en el 9 al 18 % del genoma y pueden modificar los niveles de expresión de mRNA y proteína codificados por genes cercanos a su ubicación. Poco se conoce acerca de su contribución en la patogénesis de las enfermedades metabólicas, por lo cual es necesario caracterizar estas variaciones para que potencialmente sean utilizadas como biomarcadores genéticos de riesgo de DT2.