A DNA microarray-based assay to detect dual infection with two dengue virus serotypes.

Here; we have described and tested a microarray based-method for the screening of dengue virus (DENV) serotypes. This DNA microarray assay is specific and sensitive and can detect dual infections with two dengue virus serotypes and single-serotype infections. Other methodologies may underestimate samples containing more than one serotype. This technology can be used to discriminate between the four DENV serotypes. Single-stranded DNA targets were covalently attached to glass slides and hybridised with specific labelled probes. DENV isolates and dengue samples were used to evaluate microarray performance. Our results demonstrate that the probes hybridized specifically to DENV serotypes; with no detection of unspecific signals. This finding provides evidence that specific probes can effectively identify single and double infections in DENV samples.

Gene flow pattern among Aedes aegypti populations in Mexico.

Patterns of gene flow vary greatly among Aedes aegypti populations throughout Mexico. The populations are panmictic along the Pacific coast, isolated by distance in northeast Mexico, and exhibit moderate gene flow across the Yucatan peninsula. Nine Ae. aegypti collections from 6 cities in Oaxaca, Mexico, were taken to examine the local patterns of gene flow. Genetic variation was examined in a 387-bp region of the nicotinamide adenine dinucleotide dehydrogenase subunit 4 mitochondrial gene (ND4) using single-strand conformation polymorphism analysis, and 3 haplotypes were detected. Cluster analysis on the linearized FST genetic distances failed to group collections in geographic proximity. Regression analysis of linear or road distances on linearized F(ST) indicated that proximal collections were as diverse as distant collections across an approximately 800-km range. The geographical distribution of the Mexican mosquito haplotype frequencies was determined for the ND4 sequences from 524 individuals from Oaxaca (this study) and 2,043 individuals from our previous studies. Herein, we report on yet another pattern dominated by genetic drift among 9 Ae. aegypti collections from 6 cities in Oaxaca, Mexico, and compare it to those reported in other regions of Mexico. Molecular analysis of variance showed that there was as much genetic variation among collections 4 km apart as there was among all collections. The numbers of haplotypes and the amount of genetic diversity among the collections from Oaxaca were much lower than detected in previous studies in other regions of Mexico and may reflect the effects of control efforts or adaptations to the altitudinal limits (1,500 m) of the species in Mexico. The geographical distribution of mosquito haplotypes in Mexico is also reported. Furthermore, based on the distribution of the mosquito haplotypes in America, we suggest that mosquito dispersion is very efficient, most likely due to commercial transportation.

Functional characterization of the disease-associated CCL2 rs1024611G-rs13900T haplotype: The role of the RNA-binding protein HuR.

CC-chemokine ligand 2 (CCL2) is involved in the pathogenesis of several diseases associated with monocyte/macrophage recruitment, such as HIV-associated neurocognitive disorder (HAND), tuberculosis, and atherosclerosis. The rs1024611 (alleles:A>G; G is the risk allele) polymorphism in the CCL2 cis-regulatory region is associated with increased CCL2 expression in vitro and ex vivo, leukocyte mobilization in vivo, and deleterious disease outcomes. However, the molecular basis for the rs1024611-associated differential CCL2 expression remains poorly characterized. It is conceivable that genetic variant(s) in linkage disequilibrium (LD) with rs1024611 could mediate such effects. Previously, we used rs13900 (alleles:_C>T) in the CCL2 3' untranslated region (3' UTR) that is in perfect LD with rs1024611 to demonstrate allelic expression imbalance (AEI) of CCL2 in heterozygous individuals. Here we tested the hypothesis that the rs13900 could modulate CCL2 expression by altering mRNA turnover and/or translatability. The rs13900 T allele conferred greater stability to the CCL2 transcript when compared to the rs13900 C allele. The rs13900 T allele also had increased binding to Human Antigen R (HuR), an RNA-binding protein, in vitro and ex vivo. The rs13900 alleles imparted differential activity to reporter vectors and influenced the translatability of the reporter transcript. We further demonstrated a role for HuR in mediating allele-specific effects on CCL2 expression in overexpression and silencing studies. The presence of the rs1024611G-rs13900T conferred a distinct transcriptomic signature related to inflammation and immunity. Our studies suggest that the differential interactions of HuR with rs13900 could modulate CCL2 expression and explain the interindividual differences in CCL2-mediated disease susceptibility.

Effect of Insulin Resistance on Abdominal Obesity, Liver Fat Infiltration, and Body Mass Index in Youngsters.

AIM: Evaluate insulin resistance (IR) as a mediator of the effect of body fat distribution on liver fat infiltration and stiffness (LSt) in young adults using structural equation modeling (SEM). METHODS: We invited 500 first year students from two universities and evaluated their family history to determine the risk for cardiometabolic disease. Of these, 174 students (age 19 ± 1 years) were assessed for total body fat percentage (BF%), LSt, fat infiltration (Coefficient attenuated parameter CAP), and serum biochemical analysis. We performed a mediation analysis using two different structural equation models to determine the relationship between BMI, BF%, abdominal obesity (AO), IR, LSt, and fat infiltration using standardized ß coefficients. The symbol "->" means "explains/causes". RESULTS: Model#1 supported that mediation analysis and had a better fit than the direct effect. AO->IR (b = 0.62, p = 0.005), AO->CAP (b = 0.63, p <0.001), and CAP->IR (b = 0.23, p = 0.007), with negligible effect of BMI on CAP and IR. Model#2 showed direct effect of BMI on LSt was a better fit than mediation. BMI->LSt (b = 0.17, p = 0.05) but no effect AO->LSt. Interestingly, LSt->IR (b = 0.18, p = 0.001), but bi-directional IR->LSt (b = 0.23, p = 0.001). CONCLUSIONS: AO and BMI in young adults have differential phenotypic effects on liver CAP and LSt. Visceral fat had a direct effect on IR and CAP. Meanwhile, BMI was associated with LSt. Our findings shed light on the complex interplay of factors influencing liver stiffness, particularly in young individuals. Further research is needed to elucidate the precise mechanisms underlying these associations and their implications for liver health.

Mexican mestizo population sub-structure: effects on genetic and forensic statistical parameters.

Since Mexican mestizos are an admixed population, it is necessary to determine the effects that the substructure of the population has on genetic and forensic parameters. With this aim, a study was performed with 15 STR loci (CODIS plus D2S1338 and D19S433) on 1,640 unrelated Mexican mestizos. We determine allele and genotypic frequencies observing departure from Hardy-Weinberg expectation (12 out of 15 loci, with an excess of homozygotes, Fis > 0), as well as pairs of loci in an apparent linkage disequilibrium (13 of 92 loci). We conducted a test for genetic population stratification, the results show that the Mexican mestizo population is substructured into three subgroups, which are in HW and linkage equilibrium. The combination of the 15 loci in the whole population has high forensic efficiency with the capacity to genetically discriminate one individual in one quintillion (1/10(18)). Our data potentially validates the use of these 15 STR loci to establish forensic identity and parentage testing for legal purposes, and offers a powerful tool for genetic variation analysis. However, given that the population is stratified, we highly recommend applying a correction with the inbreeding coefficient in calculations of paternity and forensic studies to avoid erroneous assumptions.

Association of HIV-1 Infection and Antiretroviral Therapy With Type 2 Diabetes in the Hispanic Population of the Rio Grande Valley, Texas, USA.

The Rio Grande Valley (RGV) in South Texas has one of the highest prevalence of obesity and type 2 diabetes (T2D) in the United States (US). We report for the first time the T2D prevalence in persons with HIV (PWH) in the RGV and the interrelationship between T2D, cardiometabolic risk factors, HIV-related indices, and antiretroviral therapies (ART). The PWH in this study received medical care at Valley AIDS Council (VAC) clinic sites located in Harlingen and McAllen, Texas. Henceforth, this cohort will be referred to as Valley AIDS Council Cohort (VACC). Cross-sectional analyses were conducted using retrospective data obtained from 1,827 registries. It included demographic and anthropometric variables, cardiometabolic traits, and HIV-related virological and immunological indices. For descriptive statistics, we used mean values of the quantitative variables from unbalanced visits across 20 months. Robust regression methods were used to determine the associations. For comparisons, we used cardiometabolic trait data obtained from HIV-uninfected San Antonio Mexican American Family Studies (SAMAFS; N = 2,498), and the Mexican American population in the National Health and Nutrition Examination Survey (HHANES; N = 5,989). The prevalence of T2D in VACC was 51% compared to 27% in SAMAFS and 19% in HHANES, respectively. The PWH with T2D in VACC were younger (4.7 years) and had lower BMI (BMI 2.43 units less) when compared to SAMAFS individuals. In contrast, VACC individuals had increased blood pressure and dyslipidemia. The increased T2D prevalence in VACC was independent of BMI. Within the VACC, ART was associated with viral load and CD4+ T cell counts but not with metabolic dysfunction. Notably, we found that individuals with any INSTI combination had higher T2D risk: OR 2.08 (95%CI 1.67, 2.6; p < 0.001). In summary, our results suggest that VACC individuals may develop T2D at younger ages independent of obesity. The high burden of T2D in these individuals necessitates rigorously designed longitudinal studies to draw potential causal inferences and develop better treatment regimens.

Vaccination in the context of the COVID-19 pandemic.

In this review, we described the history of vaccination, the different types of vaccines, and how vaccination coverage has been affected by the current COVID-19 pandemic. The effectiveness of the vaccines under metabolic host conditions is analyzed, especially when people have lost their immunocompetence, such as in patients with chronic kidney disease who are in dialysis treatment. Vaccines are produced in a variety of industrial methods, modifying costs. The novel field of vaccinomics includes the set of immune responses, the satisfactory levels of neutralizing antibodies, the production of metabolites, and the induction of protein expression. Finally, an analysis is made of the confusing messages regarding vaccination that are disseminated on social networks, and general recommendations are given.

En esta revisión se describen el historial de vacunación, los diferentes tipos de vacunas y cómo la cobertura de vacunación se ha visto afectada por la pandemia actual de COVID-19. Se analiza la efectividad de las vacunas en condiciones metabólicas del huésped, especialmente cuando las personas han perdido su inmunocompetencia, como los pacientes con enfermedad renal crónica que están en tratamiento de diálisis. Las vacunas se producen con una variedad de métodos industriales, modificando los costos. El nuevo campo de la vacunómica incluye el conjunto de respuestas inmunitarias, los niveles satisfactorios de anticuerpos neutralizantes, la producción de metabolitos y la inducción de la expresión de proteínas. Finalmente, se analizan los confusos mensajes sobre vacunación que se difunden en las redes sociales y se dan recomendaciones generales.

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children.

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and ß-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and ß-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and ß-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between ß-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and ß-carotenoids rather than that of ß-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.

Looking for Crumbs in the Obesity Forest: Anti-obesity Interventions and Obesity-Associated Cardiometabolic Traits in the Mexican Population. History and Systematic Review With Meta-Analyses.

Mexicans and Mexican Americans share culture, genetic background, and predisposition for chronic complications associated with obesity and diabetes making imperative efficacious treatments and prevention. Obesity has been treated for centuries focused-on weight loss while other treatments on associated conditions like gout, diabetes (T2D), and hypertriglyceridemia. To date, there is no systematic review that synthesizes the origin of obesity clinics in Mexico and the efforts to investigate treatments for obesity tested by randomized clinical trials (RCT). We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve anti-obesity RCT through 2019 and without an inferior temporal limit. The systematic review included RCT of anti-obesity treatments in the Mexican adult population, covering alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions reporting metabolism-associated traits such as BMI, weight, waist circumference, triglycerides, glucose, among others. Only the studies with at least 3 months of treatment were included in the meta-analyses in order to reduce placebo effects. We found 634 entries, after removal of duplicates and screening the studies based on eligibility criteria, we analyzed 43 national, and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and the implemented strategies do not have replications in the population. The nutrition/behavioral interventions were difficult to blind, and most studies have medium-to-high risk of bias. Nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like pure water instead of sweet beverages decrease triglycerides and systolic blood pressure. Dark chocolate showed the highest effect for BMI and high blood pressure, and treatment with insulin increased weight in those with T2D. The study of obesity in Mexico has been on-going for more than four decades, the interest on RCT just increased until this millennium, but with small sample sizes and lack of replication. The interventions affect different cardiometabolic associated traits, which should be analyzed in detail in the population living near the Mexico-U.S. border; therefore, bi-national collaboration is desirable to disentangle the cultural effects on this population's treatment response. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020221436, identifier: CRD42020221436.

Dataset on the epidemiology and genetic diversification of dengue virus (DENV) serotypes and genotypes in Mexico.

Dengue virus (DENV) evolution has had a significant impact on disease pathogenesis, virulence, and epidemiology in Mexico. Novel genotypic variation in DENV serotypes and genotypes may influence the magnitude and severity of dengue epidemics, as evidenced by 2009 data from Veracruz State. The data presented herein is related to the publication entitled "Epidemiological Implications of the Genetic Diversification of Dengue Virus (DENV) Serotypes and Genotypes in Mexico" [1]. Raw data and trees provide epidemiological data on DENV prevalence and a comprehensive phylogeny of both representative sequences collected from an NCBI repository, and 28 additional isolates from acute-phase plasma samples diagnosed with dengue fever or severe dengue (Raw sequencing data is hosted in the public repository Mendeley Data (http://dx.doi.org/10.17632/bf2kdhhf6x.2). Phylogenetic trees for each DENV serotype (DENV-1, -2, -3 and -4) were constructed using these sequences by a maximum likelihood methodology as well as a Bayesian Markov chain Monte Carlo (MCMC) integration approach. Phylogenetic trees exhibited: (1) DENV-1, genotype V, (2) the DENV-2 Asian/American and Asian II genotypes, (3) DENV-3, genotype III, and (4) DENV-4, genotype I. This data can be beneficial for future analyses on DENV serotype and genotype structure and the introduction of novel DENV genotype sequences in the Americas, for the further elucidation of dengue etiology.

Epidemiological implications of the genetic diversification of dengue virus (DENV) serotypes and genotypes in Mexico.

Variation and clade shifts in dengue virus (DENV) genotypes are responsible for numerous dengue fever outbreaks throughout Latin America in the past decade. Molecular analyses of dengue serotypes have revealed extensive genetic diversification and the emergence of new genotypes in Brazil (DENV-4 genotype I) and elsewhere in tropical and subtropical America. The goal of the present study is to assess the extent to which the adventitious introduction of DENV genotypes and their increasing genetic diversity affects dengue epidemiology in Mexico. A nuanced sequence inspection and phylogenetic analysis of the C-prM nucleotide region of DENV was performed for specimens collecting in 2009 from the Veracruz State, Mexico. Findings were contrasted with specimens collected in adjacent years and analysed based on the epidemiological patterns reported between 1990 and 2019. Additionally, the identification process of various DENV genotypes was assessed, including: (1) DENV-1, genotype V, (2) the DENV-2 Asian/American and Asian II genotypes (3) DENV-3, genotype III, and (4) DENV-4, genotype I. This resulted in the discovery of a distinct genetic cladistic pattern for serotype DENV-2. Lastly, study findings suggest that a correlation exists between the emergence of novel genotypes and genetic diversification, with the increasing incidence of DENV infections in Mexico in 2009.

Maya gene variants related to the risk of type 2 diabetes in a family-based association study.

Mexican Maya populations have a notably high prevalence of type 2 diabetes (T2D) as a consequence of the interaction between environmental factors and a genetic component. To assess the impact of 24 single nucleotide variants (SNVs) located in 18 T2D risk genes, we conducted a family-based association evaluation in samples from Maya communities with a high incidence of the disease. A total of four hundred individuals were recruited from three Maya communities with a high T2D incidence. Family pedigrees (100) and 49 nuclear families were included. Genotyping was performed by allelic discrimination with TaqMan probes. This study also included the family-based association test (FBAT) statistic U to assess the genetic associations with T2D, and the multivariate statistical and haplotype analyses. A positive association with TD2 risk was found for WFS1 rs6446482 (p = 0.046, Z = 1.994) under an additive model, and SIRT1 rs7896005 (p = 0.038, Z = 2.073) under the dominant model. Multivariate model analysis, including T2D status, age, and body mass index (BMI), displayed significant covariance in PPARGC-1α rs8192678; SIRT1 rs7896005; TCF7L2 rs7903146 and rs122243326; UCP3 rs3781907; and HHEX rs1111875 with a P < 0.05. This study revealed an association of SIRT1 and WFS1 with T2D risk.

Data on a genome-wide association study of type 2 diabetes in a Maya population.

Maya communities have been shown to exhibit type 2 diabetes (T2D) with high prevalence compared with Mexican mestizo populations. Furthermore, some variants associated with the risk for T2D have been described. In this study, we describe the results of a pilot genome wide association study (GWAS) using 817,823 single nucleotide polymorphisms (SNPs) to identify candidate variants for replication in future studies. Herein, we present the GWAS study data, which were divided into three parts: first, 1289 ancestry informative markers (AIMs) were selected for Latino populations containing European, African, and Native American SNPs obtained from the literature; second, a GWAS hypothesis free to select candidate genes associated with T2D was performed, which identified 24 candidate genes; and third, 39 SNPs previously associated with T2D or related traits were replicated. This article is associated with the original article published in "Gene" under the title "Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population".

[Consenso experto en tiempos de COVID-19: aplicaciones del método Delphi en materia de salud].

La epidemia de COVID-19 ha modificado la cultura de la comunicación. La solución para los problemas de salud puede ser asertiva cuando es consensuada. El método Delphi es una herramienta de consenso que emplea rondas de listas de preguntas para recopilar información del conocimiento de un panel de expertos que analizan planteamientos y posibles soluciones a problemas. Se basa en la premisa de que, con la libertad del anonimato, la inteligencia combinada mejora el juicio individual y captura la opinión colectiva experta. El proceso del método es muy flexible, pues las rondas de preguntas pueden realizarse de manera presencial o remota. En este artículo se describe cómo implementar el método Delphi convencional en tiempos de confinamiento, y se analizan la utilidad y las limitaciones del método para su uso por expertos en salud para la resolución de problemas de tratamiento, diagnóstico o administrativos. Las tecnologías actuales para recolectar los datos permiten gran flexibilidad en el formato de los cuestionarios y facilitan la recopilación de la opinión experta. Gracias a su adaptabilidad, el método Delphi se está convirtiendo en una estrategia popular que involucra los ámbitos cualitativo y cuantitativo.

Acanthosis nigricans as a composite marker of cardiometabolic risk and its complex association with obesity and insulin resistance in Mexican American children.

AIM: Acanthosis nigricans (AN) is a strong correlate of obesity and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMRFs). However, the direct causal relationship of IR with AN in obesity has been debated. Therefore, we aimed to examine the complex causal relationships among the troika of AN, obesity, and IR in Mexican Americans (MAs). METHODS: We used data from 670 non-diabetic MA children, aged 6-17 years (49% girls). AN (prevalence 33%) severity scores (range 0-5) were used as a quasi-quantitative trait (AN-q) for analysis. We used the program SOLAR for determining phenotypic, genetic, and environmental correlations between AN-q and CMRFs (e.g., BMI, HOMA-IR, lipids, blood pressure, hs-C-reactive protein (CRP), and Harvard physical fitness score (PFS)). The genetic and environmental correlations were subsequently used in mediation analysis (AMOS program). Model comparisons were made using goodness-of-fit indexes. RESULTS: Heritability of AN-q was 0.75 (p<0.0001). It was positively/significantly (p<0.05) correlated with traits such as BMI, HOMA-IR, and CRP, and negatively with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMI→HOMA-IR→AN-q yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN-q simultaneously. Using complex models, BMI was associated with AN-q and IR mediating most of the CMRFs; but no relationship between IR and AN-q. CONCLUSION: Our study suggests that obesity explains the association of IR with AN, but no causal relationship between IR and AN in Mexican American children.

Multiple recombinants in two dengue virus, serotype-2 isolates from patients from Oaxaca, Mexico.

BACKGROUND: Dengue (DEN) is a serious cause of mortality and morbidity in the world including Mexico, where the infection is endemic. One of the states with the highest rate of dengue cases is Oaxaca. The cause of DEN is a positive-sense RNA virus, the dengue virus (DENV) that evolves rapidly increasing its variability due to the absence of a repair mechanism that leads to approximately one mutational event per genome replication; which results in enhancement of viral adaptation, including the escape from host immune responses. Additionally, recombination may play a role in driving the evolution of DENV, which may potentially affect virulence and cause host tropism changes. Recombination in DENV has not been described in Mexican strains, neither has been described the relevance in virus evolution in an endemic state such as Oaxaca where the four serotypes of DENV are circulating. RESULTS: To study whether there are isolates from Oaxaca having recombination, we obtained the sequence of 6 different isolates of DENV-2 Asian/American genotype from the outbreak 2005-6, one clone of the C(91)-prM-E-NS1(2400) structural genes, and 10 clones of the E gene from the isolate MEX_OAX_1656_05. Evidence of recombination was found by using different methods along with two softwares: RDP3 and GARD. The Oaxaca MEX_OAX_1656_05 and MEX_OAX_1038_05 isolates sequenced in this study were recombinant viruses that incorporate the genome sequence from the Cosmopolitan genotype. Furthermore, the clone of the E gene namely MEX_OAX_165607_05 from this study was also recombinant, incorporating genome sequence from the American genotype. CONCLUSIONS: This is the first report of recombination in DENV-2 in Mexico. Given such a recombinant activity new genomic combinations were produced, this could play a significant role in the DENV evolution and must be considered as a potentially important mechanism generating genetic variation in this virus with serious implications for the vaccines and drugs formulation as occurs for other viruses like poliovirus, influenza and HIV.

Association of common polymorphisms in the VEGFA and SIRT1 genes with type 2 diabetes-related traits in Mexicans.

INTRODUCTION: Genetic variants have been replicated for association with type 2 diabetes mellitus (T2D) and many of them with diabetes-related traits. Because T2D is highly prevalent in Mexico, this study aimed to test the association of CDKN2A/B, PPARGC1A, VEGFA, SIRT1 and UCP2 gene polymorphisms (rs10811661, rs8192678, rs2010963, rs7896005 and rs659366 respectively) with metabolic traits in 415 unrelated Mexican mestizos with T2D under three models of inheritance. MATERIAL AND METHODS: A total of 415 unrelated Mexican mestizos were genotyped by TaqMan assays. Triglycerides, cholesterol, glucose, high-density lipoprotein cholesterol (HDL-C), insulin and anthropometric measurements were determined and the HOMA-IR was calculated. Association studies were tested by the Kruskal-Wallis test, linear regression, statistical power analysis, Bonferroni correction, paired SNP analysis, and physical interaction by GeneMANIA. RESULTS: All polymorphisms were in Hardy-Weinberg equilibrium, and the association by genotype with T2D-related traits displayed nominal significance for rs8192678 with glucose (p = 0.023) and triglycerides (p = 0.013); rs2010963 with diastolic blood pressure (DBP) (p = 0.012) and cholesterol (p = 0.013); rs7896005 with DBP (p = 0.012) and insulin (p = 0.011); and rs659366 with cholesterol (p = 0.034), glucose (p = 0.031) and triglycerides (p = 0.028); and the association of rs2010963 with HDL-C (p = 0.0007) was significant. Linear regression performed with three models of inheritance, adjusted by age + sex + BMI and corrected with Bonferroni, showed a significant association of rs2010963 with HDL-C in an additive model (p = 0.007); and rs7896005 was significantly associated with DBP in the recessive model (p = 0.006). CONCLUSIONS: Rigorous analysis evidenced the association of VEGFA rs2010963 and SIRT1 rs7896005 with HDL-C and DBP respectively; these traits are known predictors of cardiovascular complications, which increase the risk of cardiovascular diseases in this population.

The ADRA2A rs553668 variant is associated with type 2 diabetes and five variants were associated at nominal significance levels in a population-based case-control study from Mexico City.

Type 2 diabetes (T2D) is a disease with a prevalence of 9.4% in Mexicans. Its etiology is complex involving environmental and genetic factors. The aim of this study was to analyse the association between PPARG rs1801282, PPARGC1A rs8192678, VEGFA rs2010963, ADRA2A rs553668, KCNQ1 rs2237892, SIRT1 rs7896005, IGF2BP2 rs4402960, and UCP3 rs3781907 single nucleotide variants (SNVs) with T2D and metabolic traits in a case-control study of a population from Mexico City. A total of 831 blood samples of non-diabetic, with healthy control participants (416) and individuals with T2D (415) were collected over a five-year period. After DNA extraction, genotyping was performed with TaqMan probes using real-time PCR. The genotypes were analysed for association with T2D in linear and logistic regressions adjusting for age, sex, and body mass index using the dominant, recessive, and additive models with a Bonferroni correction for multiple comparisons p < 0.001 and for association with related T2D traits fixed with a p < 2.3 × 10-4. The univariate analysis gives a significant (p < 1 × 10-4) for sex, triglycerides, and HOMA-IR. Significant association with T2D was found for ADRA2A rs553668 under the recessive model (OR = 3.640 and 95% CI of 2.330-5.690 (p < 1 × 10-4); statistical power 0.999) and under the additive model (OR = 1.640 and 95% CI of 1.340-2.000 (p < 1 × 10-4); statistical power 0.997). Variants PPARG rs1801282, PPARGC1A rs8192678, SIRT1 rs7896005, IGF2BP2 rs4402960 and UCP3 rs3781907 were nominally associated (p > 0.001 and <0.050). Results describe association of ADRA2A rs553668 with T2D in a Mexican population. Variants with nominal association with T2D require to be replicated in additional Mexican populations.

Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population.

Type 2 diabetes mellitus (T2D) is one of the two leading causes of mortality in Mexico. However, most studies have focused on Caucasians or Asians, and there are a small number of studies investigating Maya populations. Furthermore, to the best of our knowledge, there is no information on isolated Maya communities with T2D frequencies of 20% that are primarily attributed to ethnicity. Consequently, this study focused on assessing which genetic risk variants could be involved in the high rates of T2D in 92 individuals with Maya ancestry; 47 were diagnosed with T2D, and 45 were classified as healthy individuals. A pilot genome-wide association study was performed using the Affymetrix Axiom Genome-wide LAT1 array. The population structure was determined with the ADMIXTURE software using 1289 Latin American selected polymorphisms, and 39 polymorphisms associated with T2D were included for replication. Association tests were performed using the Statistical Analysis System (SAS) using the allelic, genotype and Armitage trend tests. The results indicated that population structure analysis displayed no differences between T2D patients and healthy individuals; 24 loci located were identified for probable association with T2D (p > 1.288 × 10-7 and p < 1.348 × 10-4); the polymorphism AGTR2 rs1914711 in chromosome X was identified by the allele test (OR = 6.824; p = 1.448 × 10-9) as a candidate gene for association with T2D; and ARL15 rs4311394 was associated as a T2D protector by genotype and the Armitage trend test (OR = 0.318; p = 0.001). In conclusion, this study proposes 24 candidate SNPs associated with T2D for replication studies and one for protective association with T2D.

The four serotypes of dengue recognize the same putative receptors in Aedes aegypti midgut and Ae. albopictus cells.

BACKGROUND: Dengue viruses (DENV) attach to the host cell surface and subsequently enter the cell by receptor-mediated endocytosis. Several primary and low affinity co-receptors for this flavivirus have been identified. However, the presence of these binding molecules on the cell surface does not necessarily render the cell susceptible to infection. Determination of which of them serve as bona fide receptors for this virus in the vector may be relevant to treating DENV infection and in designing control strategies. RESULTS: (1) Overlay protein binding assay showed two proteins with molecular masses of 80 and 67 kDa (R80 and R67). (2) Specific antibodies against these two proteins inhibited cell binding and infection. (3) Both proteins were bound by all four serotypes of dengue virus. (4) R80 and R67 were purified by affinity chromatography from Ae. aegypti mosquito midguts and from Ae albopictus C6/36 cells. (5) In addition, a protein with molecular mass of 57 kDa was purified by affinity chromatography from the midgut extracts. (6) R80 and R67 from radiolabeled surface membrane proteins of C6/36 cells were immunoprecipitated by antibodies against Ae. aegypti midgut. CONCLUSION: Our results strongly suggest that R67 and R80 are receptors for the four serotypes of dengue virus in the midgut cells of Ae. aegypti and in C6/36 Ae. albopictus cells.