The impact of short-chain fatty acid-producing bacteria of the gut microbiota in hyperuricemia and gout diagnosis.

INTRODUCTION/OBJECTIVES: Persistent hyperuricemia is a key factor in gout; however, only 13.5% of hyperuricemic individuals manifest the disease. The gut microbiota could be one of the many factors underlying this phenomenon. We aimed to assess the difference in taxonomic and predicted functional profiles of the gut microbiota between asymptomatic hyperuricemia (AH) individuals and gout patients. METHODS: The V3-V4 region of the 16S rRNA gene of the gut microbiota of AH individuals, gout patients, and controls was sequenced. Bioinformatic analyses were carried out with QIIME2 and phyloseq to determine the difference in the relative abundance of bacterial genera among the study groups. Tax4fun2 was used to predict the functional profile of the gut microbiota. RESULTS: AH individuals presented a higher abundance of butyrate- and propionate-producing bacteria than gout patients; however, the latter had more bacteria capable of producing acetate. The abundance of Prevotella genus bacteria was not significantly different between the patients but was higher than that in controls. This result was corroborated by the functional profile, in which AH individuals had less pyruvate oxidase abundance than gout patients and less abundance of an enzyme that regulates glutamate synthetase activation than controls. CONCLUSION: We observed a distinctive taxonomic profile in AH individuals characterized by a higher abundance of short-chain fatty acid-producing bacteria in comparison to those observed in gout patients. Furthermore, we provide scientific evidence that indicates that the gut microbiota of AH individuals could provide anti-inflammatory mediators, which prevent the appearance of gout flares. Key Points • AH and gout patients both have a higher abundance of Prevotella genus bacteria than controls. • AH individuals' gut microbiota had more butyrate- and propionate-producing bacteria than gout patients. • The gut microbiome of AH individuals provides anti-inflammatory mediators that could prevent gout flares.

Severe Quantitative Scale of Acanthosis Nigricans in Neck is Associated with Abdominal Obesity, HOMA-IR, and Hyperlipidemia in Obese Children from Mexico City: A Cross-Sectional Study.

Background: Acanthosis nigricans (AN) is a clinical sign that commonly occurs in obesity; however, its specificity and sensitivity have been controversial. It is unknown if AN severity degree can be a useful marker for cardiometabolic disorders screening. We suggest that the stratified analysis of AN severity degree in neck by Burke's scale could be a useful tool in the screening of cardiometabolic alterations in obese children. Objective: The aim of this study was the association of AN severity degree in neck by Burke's scale with anthropometric, biochemical, and inflammatory parameters in obese school-age children from Mexico City. Methods: A cross-sectional study was conducted, including 95 obese school-age children stratified by AN severity degree in neck by Burke's scale. Anthropometric and fasting biochemical measurements were determined. Variables were compared by x 2 test for frequencies and one-way ANOVA with Bonferroni posttest for continuous variables. Linear regression analysis adjusted by gender, BMI, and age was performed to evaluate the association between AN severity degree and cardiometabolic alterations. Statistical significance was set at p < 0.05. Results: As AN severity degree in neck by Burke's scale increased, diastolic blood pressure (p=0.001) and triglycerides (p=0.02) significantly increased and adiponectin significantly decreased (p=0.02). Positive associations between grade 3 AN and waist circumference, HOMA-IR, triglycerides, total cholesterol, and LDL cholesterol were observed. Conclusion: Our findings could be used to identify an easier clinical tool to prevent obesity progression and its complications in pediatrics. There are no similar studies.

Infant feeding, appetite and satiety regulation, and adiposity during infancy: a study design and protocol of the 'MAS-Lactancia' birth cohort.

INTRODUCTION: The prevalence of childhood obesity has risen dramatically in recent years. A proportion of this burden has been attributed to factors that occur during the first 1000 days of life such as genetic predisposition, breast feeding and complementary feeding. Although the mechanisms by which these factors affect weight and adiposity are less well understood, appetite and satiety regulation may be a key to understanding them. This cohort study aims to investigate the role of appetite and satiety regulation as a mediator in the association between infant feeding practices and genetic polymorphisms with children's growth, adiposity and metabolic risk factors. METHODS AND ANALYSIS: 'MAS-Lactancia' (the first word means 'more' and is also an acronym in Spanish for 'Appetite and Satiety Mechanisms', the second word is 'breastfeeding') is an open, ongoing, prospective birth cohort that began the enrolment in 2016 of mother-child pairs affiliated to the Mexican Social Security Institute and that live in the city of Cuernavaca, Mexico. Pregnant women between 16-week and 22-week gestation are followed during the second half of their pregnancies, at birth and throughout their infant's first 48 months of life (at 1 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months and 48 months) at the clinic and at-home visits that include questionnaires, anthropometric measurements and biospecimen collection. The main exposure variables are infant feeding (breast feeding and complementary feeding) and genetic polymorphisms (fat mass and obesity-associated, leptin and adiponectin genes). Outcome variables include infant's growth, adiposity and metabolic risk factors. We will conduct longitudinal models and path analyses to identify the potential mediating role of satiety and appetite indicators (leptin, adiponectin, insulin concentrations, appetite and satiety perception). ETHICS AND DISSEMINATION: The study protocol, data collection instruments, consent forms and procedures were approved by the institutional review boards of the National Institute of Public Health and the Mexican Social Security Institute in Mexico. Findings will be disseminated through conferences, peer-reviewed publications and meetings with stakeholders.

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

OBJECTIVE: To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. METHODS: Hypervariable V3-V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profiles using bioinformatics in order to identify differences in taxonomy and metabolic pathways. RESULTS: We identified a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifidobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabolism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed differences in key bacterial enzymes involved in urate synthesis, degradation, and elimination. CONCLUSION: Our findings revealed that taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

Bovine Interferon-Tau Activates Type I interferon-Associated Janus-signal Transducer in HPV16-positive Tumor Cell.

The mechanisms of signal transduction by interferon-tau (IFN-τ) are widely known during the gestation of ruminants. In trophoblast cells, IFN-τ involves the activation of the JAK-STAT pathway, and it can have effects on other cell types, such as tumor cells. Here we report that the HPV16-positive BMK-16/myc cell treated with ovine IFN-τ, results in the activation of the canonical JAK-STAT and non-canonical JAK-STAT pathway. The MAPK signaling pathway was activated, we detected the proteins MEK1, MEK2, Raf1, STAT3, STA4, STAT5 and STAT6. Moreover, IFN-τ induced the expression of MHC Class I, MX and IP10 in the tumor cells and this response may be associated with the viral replication and with the anti-proliferative and the immunoregulatory effects of IFN-τ.

High Relative Abundance of Lactobacillus reuteri and Fructose Intake are Associated with Adiposity and Cardiometabolic Risk Factors in Children from Mexico City.

In Mexico, 3 of 10 children are overweight. Fructose intake and relative abundance (RA) of Lactobacillus reuteri (L. reuteri) in the intestinal microbiota are associated with obesity and diabetes in adults, but studies in children are limited. This study evaluates the association between fructose intake and L. reuteri RA with adiposity and cardiometabolic risk markers in Mexican children dietary information, microbiota profiles, adiposity indicators (Body Mass Index, BMI and Waste Circumference, WC), and cardiometabolic markers were analyzed in 1087 children aged 6-12 years. Linear regression and path analysis models were used. High-tertile fructose intake and L. reuteri RA were positively associated with BMI (ßTertil 3 vs. Tertil 1 = 0.24 (95% CI, 0.04; 0.44) and ßT3 vs. T1 = 0.52 (95% CI, 0.32; 0.72)) and WC (ßT3 vs. T1 = 2.40 (95% CI, 0.93; 3.83) and ßT3 vs. T1 = 3.40 (95% CI, 1.95; 4.90)), respectively. Also, these factors mediated by adiposity were positively correlated with high triglycerides and insulin concentrations and HOMA-IR (p ≤ 0.03) and negatively associated with HDL-C concentration (p < 0.01). High-tertile fructose intake and L. reuteri RA were directly associated with adiposity and indirectly associated though adiposity with metabolic disorders in children. In conclusion, fructose intake and L. reuteri RA were directly associated with adiposity and indirectly associated with metabolic disorders in children, mediated by adiposity.

Contribution of MSMB promoter region gene polymorphism to early-onset prostate cancer risk in Mexican males.

Sexually transmitted infections and its contribution to prostate cancer (PC) development have been relevant in different populations. MSMB gene polymorphism (rs10993994) has exhibited an association both with PC as well as the susceptibility to sexually transmitted infections. Hitherto, these conditions have been not studied in Mexico yet, neither if sexually transmitted infections could modify the MSMB and PC association. Herein, socio-demographic features, sexually transmitted infections records, the reproductive backgrounds, and the genetic characterisation were analysed in 322 incident PC cases and 628 population healthy controls from Mexico City. Whole PC, early-onset PC (PC at < 60 years old), late-onset PC (≥ 60 years old), and PC aggressiveness were used to evaluate the genetic variants contribution to PC risk using unconditional logistic regression models. Overall, none associations between the allelic variants of rs10993994 polymorphisms with whole and PC aggressiveness were found. Howbeit, the TT genotype carriers presented the highest susceptibility to develop early-onset PC (OR = 2.66; 95% CI = 1.41, 5.04; p = 0.03) than CC+CT carriers, both with codominant and recessive models. Although none association between whole PC and MSMB gene polymorphism was found, our results were reinforced by prior studies in European descendent populations, suggesting a contribution between rs10993994 and early-onset PC development.

Genetic contribution to waist-to-hip ratio in Mexican children and adolescents based on 12 loci validated in European adults.

BACKGROUND/OBJECTIVES: The prevalence of abdominal obesity in Mexican children has risen dramatically in the past decade. Genome-wide association studies (GWAS) for waist-to-hip ratio (WHR) performed predominantly in European descent adult  populations have identified multiple single-nucleotide polymorphisms (SNPs) with larger effects in women. The contribution of these SNPs to WHR in non-European children is unknown. SUBJECTS/METHODS: Mexican children and adolescents (N = 1421, 5-17 years) were recruited in Mexico City. Twelve GWAS SNPs were genotyped using TaqMan Open Array and analyzed individually and as a gene score (GS). RESULTS: Mexican boys and girls displayed 2.81 ± 0.29 and 3.10 ± 0.31 WHR standard deviations higher than children and adolescents from the United States. WHR was positively associated with TG (ß = 0.733 ± 0.190, P = 1.1 × 10-4) and LDL-C (ß = 0.491 ± 0.203, P = 1.6 × 10-2), and negatively associated with HDL-C (ß = -0.652 ± 0.195, P = 8.0 × 10-4), independently of body mass index. The effect allele frequency (EAF) of 8 of 12 (67%) SNPs differed significantly (P < 4.17 × 10-3) in Mexican children and European adults, with no evidence of effect allele enrichment in both populations (4 depleted and 4 enriched; binomial test, P = 1). Ten out of 12 SNPs (83.3%) had effects that were directionally consistent with those reported in GWAS (P = 0.04). HOXC13 rs1443512 displayed the best fit when modeled recessively, and was significantly associated with WHR under a recessive mode of inheritance (ß = 0.140 ± 0.06, P = 2.3 × 10-2). Significant interactions with sex were also observed for HOXC13 rs1443512 and the GS on WHR (P = 2.2 × 10-2 and 1.2 × 10-2, respectively). HOXC13 rs1443512 (ß = 0.022 ± 0.012, P = 4.7 × 10-2) and the GS (ß = 0.007 ± 0.003, P = 7.0 × 10-3) were significantly associated with WHR in girls only. CONCLUSIONS: This study demonstrates that Mexican children are at high risk for abdominal obesity and detrimental lipid profiles. Our data support a partial transferability of sex-specific European GWAS WHR association signals in children and adolescents from the admixed Mexican population.

Estudio de validación de cuatro diferentes criterios para el diagnóstico de síndrome metabólico en población infantil / Validation study of four different criteria for the diagnosis of metabolic syndrome in children

Resumen Introducción: El síndrome metabólico (SM) es un problema de salud pública, el cual no cuenta con estrategias adecuadas de prevención, diagnóstico y tratamiento para población infantil. Los criterios existentes son controversiales y no son aplicables en los niños. Asimismo, varían según autores y comités de expertos; lo que podría tener importantes consecuencias en el diagnóstico de SM, impactando el tratamiento oportuno y el pronóstico del individuo. Objetivo: Validar criterios (NCEP-ATPIII; Cook, Ford y Duncan, et al; Ferranti, et al; Cruz, et al; e IDF1) para el diagnóstico de SM en niños mexicanos. Metodología: Estudio transversal de 2599 niños entre 6 y 16 años, residentes de la Ciudad de México. Se consideró SM con tres o más de los cinco componentes en los distintos criterios; y dos o más componentes con la presencia de obesidad central para IDF. Se consideró como Gold Standard la combinación de los cinco criterios diagnósticos. Para identificar el mejor valor predictivo se calculó sensibilidad, especificidad, valor predictivo positivo (VPP), valor predictivo negativo (VPN) y razón de verosimilitud. Resultados: Se observó una mayor proporción de individuos diagnosticados con SM con el criterio de Ferranti, et al. en comparación con los demás criterios evaluados. Nuestra propuesta ad hoc presentó una alta sensibilidad (0,89) y especificidad (0,90) frente al Gold Standard aplicado. Conclusión: El criterio propuesto por nosotros contiene una elección de componentes sencillos y de bajo costo, que facilitará su aplicación, permitiendo la unificación en el diagnóstico, tratamiento y pronóstico poblacional, reduciendo los índices de morbimortalidad en mexicanos.

Abstract Introduction: Metabolic syndrome (MS) is a public health problem without appropriate strategies for prevention, diagnosis and treatment in children. Existing criteria are controversial and not applicable for pediatric population, with variations according to different authors and expert committees, which could have important consequences in MS diagnosis, treatment and prognosis. Objective: To validate different definitions (NCEP-ATPIII; Cook, Ford and Duncan, et al; Ferranti, et al; Cruz, et al; and IDF1) for metabolic syndrome diagnosis in Mexican children. Methodology: Cross-sectional study of 2599 children aged between 6 and 16 years, residents of Mexico City. MS was defined as the presence of three or more of the five components in the different criteria; and two or more components with the presence of central obesity for IDF. The Gold Standard was considered as the combination of the five diagnostic criteria. To identify the best predictive value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratio were calculated. Results: A greater proportion of individuals diagnosed with the Ferranti, et al criterion was observed in comparison with the other criteria evaluated. We proposed an ad hoc criteria which showed a high sensitivity (0,89) and specificity (0,90) compared to the Gold Standard applied. Conclusion: Our diagnostic criteria contains a choice of simple and low-cost components that will facilitate its application in health institutions and will unify-diagnostic criteria, treatment, and prognosis, reducing morbidity and mortality rates in Mexican population.

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.

Dietary patterns in Mexican children and adolescents: Characterization and relation with socioeconomic and home environment factors.

BACKGROUND: Eating habits in children and adolescents are influenced by multiple determinants, which include socioeconomic and home environmental factors. OBJECTIVE: To characterize the dietary patterns in Mexican children and adolescents and to assess its association with socioeconomic and home environmental factors. METHODS: A cross-sectional study was conducted in 878 children and adolescents aged 5-15 years, unrelated, selected randomly from Morelos Sports Unit at north of Mexico City. Dietary, anthropometric, family, and socioeconomic information was obtained from each participant. Dietary patterns were identified through cluster analysis. The association between dietary patterns with socioeconomic and home environmental factors was assessed by a multivariate multinomial logistic regression model. RESULTS: Three major dietary patterns were identified: diverse dietary pattern (D), high fat dietary pattern (HF), and high sugar dietary pattern (HS). 87% of the participants followed the HF or HS dietary patterns (36% & 51%, respectively). Mother's occupation and the child's screen time was associated with a significant likelihood of following a HF and HS dietary patterns. CONCLUSION: A high percentage of children and adolescents reported following a HS or HF dietary pattern, which in turn were associated with socioeconomic and home environmental factors. These results suggests priority groups for prevention and control actions.

TLR9 gene polymorphism -1486T/C (rs187084) is associated with uterine cervical neoplasm in Mexican female population.

PURPOSE: The aim of this work was to evaluate the association of single nucleotide polymorphisms in TLR9 (-1486 T/C [rs187084], -1237T/C [rs5743836] and G2848A [rs352140]) with HPV infection, squamous intraepithelial lesions, and uterine cervical neoplasm in a Mexican population. Additionally, the peripheral expression of TLR9 was evaluated to evaluate the differences in the TLR9 expression associated with every genotype in the locus -1486 of the TLR9 gene. The serum concentration of TLR9 was evaluated in a randomly selected subsample. METHODS: Genotyping was performed using predesigned 5' endonuc lease assays and the association of the polymorphisms with the diagnosis groups were assessed by performing multinomial regression models. The relative expression of TLR9 in peripheral blood mononuclear cells was evaluated by real-time polymerase chain reaction and the association of the level of TLR9 expression with the diagnosis was evaluated by performing multinomial regression models. The serum concentration of TLR9 was evaluated in a subsample of patients diagnosed with uterine cervical neoplasm by ELISA. RESULTS: The results showed that genotype TT in the -1486 locus of TLR9 was significantly associated with HPV infection (OR = 3.25, 95% CI 1.12-9.46), squamous intraepithelial cervical lesion (OR = 3.76, 95% CI 1.36-10.41), and uterine cervical neoplasm (OR = 5.30, 95% CI 1.81-15.55). Moreover, the highest level of TLR9 expression was significantly associated with a greater risk for developing squamous intraepithelial cervical lesion and uterine cervical neoplasm. The serum TLR9 concentration was higher in patients with uterine cervical cancer than in controls. CONCLUSION: Our findings indicate that genotype TT in the -1486 locus of the TLR9 gene could comprise a risk genotype for HPV infection, squamous intraepithelial cervical lesion, and uterine cervical neoplasm in Mexican female population. Further studies with larger samples are needed to evaluate if the peripheral expression of TLR9 could be used as a biomarker of uterine cervical neoplasm progression.

Role of TLR9 in Oncogenic Virus-Produced Cancer.

Nucleic acid recognition by toll-like receptor 9 (TLR9) initiates signaling pathways that regulate the production of proinflammatory cytokines or type I interferons, as well as many other molecules required to initialize the immune response. The use of synthetic oligodeoxynucleotides (ODNs) has been crucial to emulate the recognition of DNA sequences by TLR9. Furthermore, ODN administration to mice has shown to confer protection against a wide range of viral, bacterial, and parasitic pathogens. In contrast, oncogenic DNA viruses like hepatitis B virus, Epstein-Barr virus, and human papilloma virus inhibit TLR9 expression, thus contributing to the establishment of chronic viral infections. In this review, we will focus on TLR9 signals initiated by ODN recognition, on the inhibition of TLR9 expression mediated by DNA oncogenic viruses, and on TLR9 expression as a relevant event in the progression to cancer, considering other functions of this receptor, aside from viral recognition.

Expression of candidate genes associated with obesity in peripheral white blood cells of Mexican children.

INTRODUCTION: Obesity is a chronic, complex, and multifactorial disease, characterized by excess body fat. Diverse studies of the human genome have led to the identification of susceptibility genes that contribute to obesity. However, relatively few studies have addressed specifically the association between the level of expression of these genes and obesity. MATERIAL AND METHODS: We studied 160 healthy and obese unrelated Mexican children aged 6 to 14 years. We measured the transcriptional expression of 20 genes associated with obesity, in addition to the biochemical parameters, in peripheral white blood cells. The detection of mRNA levels was performed using the OpenArray Real-Time PCR System (Applied Biosystems). RESULTS: Obese children exhibited higher values of fasting glucose (p = 0.034), fasting insulin (p = 0.004), low-density lipoprotein (p = 0.006), triglycerides (p < 0.001), systolic blood pressure and diastolic blood pressure (p < 0.001), and lower values of high-density lipoprotein (p < 0.001) compared to lean children. Analysis of transcriptional expression data showed a difference for ADRB1 (p = 0.0297), ADIPOR1 (p = 0.0317), GHRL (p = 0.0060) and FTO (p = 0.0348) genes. CONCLUSIONS: Our results suggest that changes in the expression level of the studied genes are involved in biological processes implicated in the development of childhood obesity. Our study contributes new perspectives for a better understanding of biological processes involved in obesity. The protocol was approved by the National Committee and Ethical Committee Board from the Mexican Social Security Institute (IMSS) (IMSS FIS/IMSS/PRIO/10/011).

Evaluating the transferability of 15 European-derived fasting plasma glucose SNPs in Mexican children and adolescents.

Genome wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) that are associated with fasting plasma glucose (FPG) in adult European populations. The contribution of these SNPs to FPG in non-Europeans and children is unclear. We studied the association of 15 GWAS SNPs and a genotype score (GS) with FPG and 7 metabolic traits in 1,421 Mexican children and adolescents from Mexico City. Genotyping of the 15 SNPs was performed using TaqMan Open Array. We used multivariate linear regression models adjusted for age, sex, body mass index standard deviation score, and recruitment center. We identified significant associations between 3 SNPs (G6PC2 (rs560887), GCKR (rs1260326), MTNR1B (rs10830963)), the GS and FPG level. The FPG risk alleles of 11 out of the 15 SNPs (73.3%) displayed significant or non-significant beta values for FPG directionally consistent with those reported in adult European GWAS. The risk allele frequencies for 11 of 15 (73.3%) SNPs differed significantly in Mexican children and adolescents compared to European adults from the 1000G Project, but no significant enrichment in FPG risk alleles was observed in the Mexican population. Our data support a partial transferability of European GWAS FPG association signals in children and adolescents from the admixed Mexican population.

Assessing the effects of 35 European-derived BMI-associated SNPs in Mexican children.

OBJECTIVE: The prevalence of obesity in Mexico has increased at an alarming rate in both adults and children. This study was undertaken to test in Mexican children the effects of single nucleotide polymorphisms (SNP) that have been associated with body mass index (BMI) and obesity in Europeans. METHODS: School-age children (N = 1,559, 5-17 years) were recruited in Mexico City. Thirty-five SNPs with established effects on BMI and obesity were genotyped and analyzed individually and as a combined gene score (GS). RESULTS: SNPs in FAIM2 (rs7138803), GPRC5BB (rs12444979), MTIF3 (rs4771122), TFAP2B (rs987237), TMEM18 (rs7561317), and the GS were significantly associated with BMI. The GS explained 0.9% of the variance of BMI. Also, SNPs in LRRN6C (rs10968576) and MC4R (rs17782313) were significantly associated with overweight and obesity categories, respectively. Importantly, the effect allele frequency of 26/35 SNPs (74.3%) differed significantly between Mexican children and European adults. No significant gene × environment or gene × gene interactions were detected after Bonferroni adjustment. CONCLUSIONS: Several SNPs first associated with BMI/obesity in European adults replicated well in Mexican children, and investigating differences in the distribution of effect alleles across ethnic populations may shed light on genetic susceptibilities of different populations to obesity.

Genetic markers of inflammation may not contribute to metabolic traits in Mexican children.

BACKGROUND: Low-grade chronic inflammation is a common feature of obesity and its cardio-metabolic complications. However, little is known about a possible causal role of inflammation in metabolic disorders. Mexico is among the countries with the highest obesity rates in the world and the admixed Mexican population is a relevant sample due to high levels of genetic diversity. METHODS: Here, we studied 1,462 Mexican children recruited from Mexico City. Six genetic variants in five inflammation-related genes were genotyped: rs1137101 (leptin receptor (LEPR)), rs7305618 (hepatocyte nuclear factor 1 alpha (HNF1A)), rs1800629 (tumor necrosis factor alpha (TNFA)), rs1800896, rs1800871 (interleukin-10 (IL-10)), rs1862513 (resistin (RETN)). Ten continuous and eight binary traits were assessed. Linear and logistic regression models were used adjusting for age, sex, and recruitment centre. RESULTS: We found that one SNP displayed a nominal evidence of association with a continuous trait: rs1800871 (IL-10) with LDL (beta = -0.068 ± 1.006, P = 0.01). Subsequently, we found one nominal association with a binary trait: rs7305618 (HNF1A) with family history of hypertension (odds-ratio = 1.389 [1.054-1.829], P = 0.02). However, no P-value passed the Bonferroni correction for multiple testing. DISCUSSION: Our data in a Mexican children population are consistent with previous reports in European adults in failing to demonstrate an association between inflammation-associated single nucleotide polymorphisms (SNPs) and metabolic traits.

Androgen receptor CAG polymorphism and sporadic and early-onset prostate cancer among Mexican men.

A short CAG repeat length in the gene encoding for the androgen receptor (AR) has been associated with prostate cancer (PC) risk and aggressiveness. In Latino men, information on this association is scarce. Hence, the aim of this study was to evaluate this association in Mexican males. Using fragment analysis by capillary electrophoresis, we determined the number of CAG repeats-(CAG)n-in AR gene from 158 incident PC cases and 326 age-matched healthy controls (±5 years), residing in Mexico City, Mexico. According to Gleason scale and age at diagnosis, cases were classified as high (⩾7) and low grade (<7), as well as early onset (<60 years) or late onset PC (⩾60 years). At diagnosis, 78% of cases were classified as high-grade and 26.6% as early onset. Men with sporadic (no family history of PC) and early-onset PC presented shorter CAG repeat length than controls (18.6±2.2 vs 19.5±2.5; P=0.02). Lower number of CAG repeats (CAG)⩽19 were associated with a greater risk for early-onset PC (odds ratio: 2.31; 95% confidence interval: 1.14-4.69). CAG repeat length could increase the risk for sporadic and early-onset PC. The best cutoff point for identifying at-risk subjects was (CAG)19. However, further studies are necessary to replicate our findings in subjects with a family history of PC and also to evaluate the association between CAG repeats length and disease progression.

Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study.

Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-ß1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a ß-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When ß-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-ß1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings.