Environmental and Genetic Risk Factors in Developmental Dysplasia of the Hip for Early Detection of the Affected Population.

Diagnosis of developmental dysplasia of the hip (DDH) mostly relies on physical examination and ultrasound, and both methods are operator-dependent. Late detection can lead to complications in young adults. Current evidence supports the involvement of environmental and genetic factors, such as single nucleotide variants (SNVs). Incorporating genetic factors into diagnostic methods would be useful for implementing early detection and management of affected individuals. Our aim was to analyze environmental factors and SNVs in DDH patients. We included 287 DDH cases and 284 controls. Logistic regression demonstrated an association for sex (OR 9.85, 95% CI 5.55-17.46, p = 0.0001), family history (OR 2.4, 95% CI 1.2-4.5, p = 0.006), fetal presentation (OR 3.19, 95% CI 1.55-6.54, p = 0.002), and oligohydramnios (OR 2.74, 95%CI 1.12-6.70, p = 0.026). A model predicting the risk of DDH including these variables showed sensitivity, specificity, PPV, and NPV of 0.91, 0.53, 0.74, and 0.80 respectively. The SNV rs1800470 in TGFB1 showed an association when adjusted for covariables, OR 0.49 (95% CI 0.27-0.90), p = 0.02. When rs1800470 was included in the equation, sensitivity, specificity, PPV and NPV were 0.90, 0.61, 0.84, and 0.73, respectively. Incorporating no-operator dependent variables and SNVs in detection methods could be useful for establishing uniform clinical guidelines and optimizing health resources.

Association between soft drinks intake and low glomerular filtration rate in Mexican adults: Results from RenMex.

BACKGROUND & AIMS: To evaluate the association between soft drinks (SDs) consumption and estimated glomerular filtration rate (eGFR) in a Mexican adult population. METHODS: We used data from the RenMex consortium (n = 2095) that included the Mexican Teachers Cohort Study (34-65 years), the Health Workers Cohort Study (18-90 years), and the Comitán Study (19-91 years). In this cross-sectional study, we assessed SDs consumption (cola and flavored soda) using a food frequency questionnaire (FFQ) and estimated eGFR using the CKD Epidemiology Collaboration equation. Quantile regression was used to assess the association between SDs consumption and eGFR with eGFR as a continuous variable. Multinomial logistic regression models were used for eGFR categories derived from quantile regression (mildly decreased eGFR, ≥72.9-87.9 mL/min/1.73 m2 and moderately decreased eGFR, <72.9 mL/min/1.73 m2). RESULTS: Mean age of study participants was 47.2 years, 67.5% were women, and 12.2% had diabetes. eGFR was <60 mL/min/1.73 m2 in 3.7% of study participants. Mildly decreased eGFR was present in 14.8%, and moderately decreased eGFR was present in 10.1% of study participants. Quantile regression results showed that SDs consumption was associated with lower eGFR at the 10th, 25th, 50th and 75th percentile. Based on the final adjusted multinomial model, ≥7 servings/week was positively associated with moderately decreased eGFR relative to <1 serving/week (Relative Risk Ratio = 1.95; 95% CI: 1.07-3.57). CONCLUSION: Our results suggest that higher SDs consumption is associated with lower eGFR. Encouraging healthy dietary choices should be part of the management and prevention of CKD.

Hypoxia Induces Alterations in the Circadian Rhythm in Patients with Chronic Respiratory Diseases.

The function of the circadian cycle is to determine the natural 24 h biological rhythm, which includes physiological, metabolic, and hormonal changes that occur daily in the body. This cycle is controlled by an internal biological clock that is present in the body's tissues and helps regulate various processes such as sleeping, eating, and others. Interestingly, animal models have provided enough evidence to assume that the alteration in the circadian system leads to the appearance of numerous diseases. Alterations in breathing patterns in lung diseases can modify oxygenation and the circadian cycles; however, the response mechanisms to hypoxia and their relationship with the clock genes are not fully understood. Hypoxia is a condition in which the lack of adequate oxygenation promotes adaptation mechanisms and is related to several genes that regulate the circadian cycles, the latter because hypoxia alters the production of melatonin and brain physiology. Additionally, the lack of oxygen alters the expression of clock genes, leading to an alteration in the regularity and precision of the circadian cycle. In this sense, hypoxia is a hallmark of a wide variety of lung diseases. In the present work, we intended to review the functional repercussions of hypoxia in the presence of asthma, chronic obstructive sleep apnea, lung cancer, idiopathic pulmonary fibrosis, obstructive sleep apnea, influenza, and COVID-19 and its repercussions on the circadian cycles.

Association Study between Antioxidant Nutrient Intake and Low Bone Mineral Density with Oxidative Stress-Single Nucleotide Variants: GPX1 (rs1050450 and rs17650792), SOD2 (rs4880) and CAT (rs769217) in Mexican Women.

Oxidative stress is essential in developing multiple bone metabolism diseases, including osteoporosis. Single-nucleotide variants (SNVs) have been associated with oxidative stress, promoting an imbalance between the production of reactive oxygen species and the ability to neutralize them, and it has been reported that antioxidant nutrient intake can influence bone mineral density (BMD). This work reports the association between oxidative stress-related SNVs (GPX1-rs1050450, rs17650792, SOD2-rs4880, and CAT-rs769217), BMD, and antioxidant nutrient intake. The study included 1269 Mexican women from the Health Workers Cohort Study. Genotyping was performed using predesigned TaqMan assays. Dietary data were collected using a 116-item semi-quantitative food frequency questionnaire. A dietary antioxidant quality score (DAQS) was used to estimate antioxidant-nutrient intake. Association analysis was estimated via linear, logistic, or quantile regression models. The results showed an association of the rs1050450-A and rs17650792-A alleles with femoral neck BMD (p = 0.038 and p = 0.017, respectively) and the SNV rs4880-A allele with total hip BMD (p = 0.026) in respondents aged 45 years or older. In addition, antioxidant-nutrient intake was associated with the rs4880-GG genotype, being significant for fiber (p = 0.007), riboflavin (p = 0.005), vitamin B6 (p = 0.034), and vitamin D (p = 0.002). The study showed an association between oxidative stress-related SNVs, BMD, and antioxidant-nutrient intake in Mexican women. Therefore, treatments for low BMD could be developed based on antioxidant supplementation.

Advanced glycation end products are associated with cardiovascular risk in the Mexican population.

BACKGROUND AND AIMS: Chronic exposure to hyperglycemia is a significant risk factor for cardiovascular disease (CVD). Advanced glycation end products (AGES) result from multiple sugar-dependent reactions interacting with proteins and their receptors, generating endothelial dysfunction and CVD. However, there is little epidemiological data about its impact on CVD risk. We aimed to assess the association between circulating AGES and CVD risk in the Mexican population. METHODS AND RESULTS: We used longitudinal data from waves 2004-2006 and 2010-2012 of 1195 participants from the Health Workers Cohort Study. Circulating AGES were assessed by radioimmunoassay, and cardiovascular risk (CVR) was computed with the Framingham risk score. Linear and logistic fixed-effects regression models were used to assess the interest association, adjusting for confounding factors. An increase in 200 µU/ml of AGES was associated with a 0.18% increased risk of CVD (95% CI 0.05-0.31%). After adjusting for physical activity and smoking status, individuals who increased their AGES category had higher odds of middle-high CVR (low to medium AGES: OR 1.83, 95% CI 1.11-3.20; low to high AGES: OR 2.61, 95% CI 1.51-4.50). The associations remained statistically significant when we further adjusted for insulin resistance, dietary intake of AGES, and total daily calorie intake. CONCLUSION: Our data show that circulating AGES are associated with the Framingham CVD risk score, independently of other major risk factors for CVD in the Mexican population.

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions.

The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5-9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: -4.0 kg (-2.9%) in patient 1, and -1.8 kg (-1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (-2.9 kg; -2.8%). Phentermine treatment produced similar weight loss in six carriers (-12.7 kg; 15.5%) and 18 non-carriers (-11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.

Functional Repercussions of Hypoxia-Inducible Factor-2α in Idiopathic Pulmonary Fibrosis.

Hypoxia and hypoxia-inducible factors (HIFs) are essential in regulating several cellular processes, such as survival, differentiation, and the cell cycle; this adaptation is orchestrated in a complex way. In this review, we focused on the impact of hypoxia in the physiopathology of idiopathic pulmonary fibrosis (IPF) related to lung development, regeneration, and repair. There is robust evidence that the responses of HIF-1α and -2α differ; HIF-1α participates mainly in the acute phase of the response to hypoxia, and HIF-2α in the chronic phase. The analysis of their structure and of different studies showed a high specificity according to the tissue and the process involved. We propose that hypoxia-inducible transcription factor 2a (HIF-2α) is part of the persistent aberrant regeneration associated with developing IPF.

Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by exacerbated extracellular matrix deposition that disrupts oxygen exchange. Hypoxia and its transcription factors (HIF-1α and 2α) influence numerous circuits that could perpetuate fibrosis by increasing myofibroblasts differentiation and by promoting extracellular matrix accumulation. Therefore, this work aimed to elucidate the signature of hypoxia in the transcriptomic circuitry of IPF-derived fibroblasts. To determine this transcriptomic signature, a gene expression analysis with six lines of lung fibroblasts under normoxia or hypoxia was performed: three cell lines were derived from patients with IPF, and three were from healthy donors, a total of 36 replicates. We used the Clariom D platform, which allows us to evaluate a huge number of transcripts, to analyze the response to hypoxia in both controls and IPF. The control's response is greater by the number of genes and complexity. In the search for specific genes responsible for the IPF fibroblast phenotype, nineteen dysregulated genes were found in lung fibroblasts from IPF patients in hypoxia (nine upregulated and ten downregulated). In this sense, the signaling pathways revealed to be affected in the pulmonary fibroblasts of patients with IPF may represent an adaptation to chronic hypoxia.

Association of Gut Microbiota with Atherogenic Dyslipidemia, and Its Impact on Serum Lipid Levels after Bariatric Surgery.

Gut microbiota has been suggested to modulate circulating lipids. However, the relationship between the gut microbiota and atherogenic dyslipidemia (AD), defined as the presence of both low HDL-C and hypertriglyceridemia, is not fully understood. Moreover, because obesity is among the main causes of secondary AD, it is important to analyze the effect of gut microbiota composition on lipid profiles after a weight loss intervention. We compared the microbial diversity and taxonomic composition in patients with AD (n = 41) and controls (n = 38) and sought correlations of genera abundance with serum lipid levels in 20 patients after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Gut microbiota composition was profiled using next-generation sequencing of 16S rRNA. Gut microbiota diversity was significantly lower in atherogenic dyslipidemia. Moreover, relative abundance of two genera with LDA score >3.5 (Megasphaera and LPS-producing Escherichia-Shigella), was significantly higher in AD subjects, while the abundance of four short chain fatty acids (SCFA) producing-genera (Christensenellaceae R-7, Ruminococcaceae UCG-014; Akkermansia and [Eubacterium] eligens group) was significantly higher in controls. Notably, [Eubacterium] eligens group abundance was also significantly associated with higher HDL-C levels in RYGB patients one year after surgery. Although dietary polyunsaturated fatty acid/saturated fatty acid (PUFA/SFA) ratio and PUFA intake were higher in controls than in AD subjects, of the four genera differentiated in cases and controls, only Akkermansia abundance showed a positive and significant correlation with PUFA/SFA ratio. Our results suggest that SCFA-producing bacteria promote a healthy lipid homeostasis, while the presence of LPS-producing bacteria such Escherichia-Shigella may contribute to the development of atherogenic dyslipidemia.

Association of Polymorphisms in Estrogen Receptor Genes (ESR1 and ESR2) with Osteoporosis and Fracture-Involvement of Comorbidities and Epistasis.

Single-nucleotide polymorphisms (SNPs) in the ESR1/ESR2 genes play a role in osteoporosis (OP). Our objective was to determine associations of polymorphisms in ESR genes with OP and fracture, SNP-SNP interactions, and involvement of comorbidities. We analyzed 170 Mexican osteoporotic women (FNOP), 173 with hip fracture (HFx), and 210 controls. The SNPs, ESR1 rs2234693CC, rs851982CC and rs1999805AA, were associated with reduced OP risk (odds ratios [ORs] = 0.35, 0.40 and 0.32, respectively; p < 0.05); rs2234693CC was associated with reduced fracture risk (OR = 0.24; p < 0.05). The obese/overweight carriers of rs9340799GG had a lower OP (OR = 0.15, p = 0.016) and fracture (OR = 0.12, p = 0.0057) risk. The rs9479055AA and rs3020404AA hypertensive carriers had a higher OP risk (OR = 5.96, p = 0.032; and OR = 5.29, p = 0.02, respectively). In addition, rs3020404AA had a higher risk of fracture (OR = 4.90, p = 0.045). The rs2228480GG hypertensive carriers had a higher risk of fracture (OR = 6.22, p = 0.0038). We found a synergic relation between the ESR1 rs3020331 and rs1999805 in femoral neck OP and HFx. The rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms are associated with a high risk forming a haplotype. The epistasis analysis suggests the contribution of both genes (ESR1/ESR2) to the risk of OP and fracture. Epistasis and involvement of obesity and hypertension lead to a significant modification of the risk.

Performance of an affordable urine self-sampling method for human papillomavirus detection in Mexican women.

INTRODUCTION: Urine self-sampling for human papillomavirus (HPV)-based cervical cancer screening is a non-invasive method that offers several logistical advantages and high acceptability, reducing barriers related to low screening coverage. This study developed and evaluated the performance of a low-cost urine self-sampling method for HPV-testing and explored the acceptability and feasibility of potential implementation of this alternative in routine screening. METHODS: A series of sequential laboratory assays examined the impact of several pre-analytical conditions for obtaining DNA from urine and subsequent HPV detection. Initially, we assessed the effect of ethylaminediaminetetraacetic acid (EDTA) as a DNA preservative examining several variables including EDTA concentration, specimen storage temperature, time between urine collection and DNA extraction, and first-morning micturition versus convenience sample collection. We further evaluated the agreement of HPV-testing between urine and clinician-collected cervical samples among 95 women. Finally, we explored the costs of self-sampling supplies as well as the acceptability and feasibility of urine self-sampling among women and healthcare workers. RESULTS: Our results revealed higher DNA concentrations were obtained when using a 40mM EDTA solution, storing specimens at 25°C and extracting DNA within 72 hrs. of urine collection, regardless of using first-morning micturition or a convenience sampling. We observed good agreement (Kappa = 0.72) between urine and clinician-collected cervical samples for HPV detection. Furthermore, urine self-sampling was an affordable method (USD 1.10), well accepted among cervical cancer screening users, healthcare workers, and decision-makers. CONCLUSION: These results suggest urine self-sampling is feasible and appropriate alternative for HPV-testing in HPV-based screening programs in lower-resource contexts.

MicroRNA expression in relation with clinical evolution of osteosarcoma.

Osteosarcoma is the most common malignant bone tumor. Early diagnosis remains a major challenge, mainly because of the lack of specific biomarkers. We performed miRNAs expression analysis through qPCR in affected and paired healthy bone derived from osteosarcoma patients. Hierarchical clustering using the top ten miRNAs with differential expression showed two main clusters. One integrated by patients with the presence of metastasis or relapse and the other without these complications. Further pathway enrichment analysis reduced to four main miRNAs, hsa-miR-486-3p, hsa-miR-355-5p, hsa-miR-34a-5p and hsa-miR-1228-3p. Afterwards, we compared patients with and without metastasis, the function enrichment analysis along with review of relevant literature, showed that hsa-miR-93-5p and hsa-miR-28-5p were associated with metastasis development. Our results support the relevance of miRNAs in the pathogenesis of osteosarcoma and contribute with evidence regarding the potential role of miRNAs as potential biomarkers. More studies are needed to define the most informative miRNAs in osteosarcoma patients.

MicroRNA-548-3p overexpression inhibits proliferation, migration and invasion in osteoblast-like cells by targeting STAT1 and MAFB.

Osteoporosis is the most common bone disease and a public health issue with increasing prevalence in Mexico. This disease is caused by an imbalance in the bone remodelling process mediated by osteoclast and osteoblast. MicroRNAs have emerged as key players during the differentiation of both types of cells specialized involved in bone metabolism. We found high expression levels of miR-548x-3p in circulating monocytes derived from postmenopausal osteoporotic women. This study aimed to analyse the functional characterization of miR-548x-3p roles in the bone remodelling process. We validated by RT-qPCR, the elevated levels of miR-548x-3p in circulating monocytes derived from osteoporosis women. Through bioinformatics analysis, we identify MAFB and STAT1 as potential target genes for miR-548x-3p. Both genes showed low levels of expression in circulating monocytes derived from osteoporotic women. In addition, we demonstrated the binding of miR-548x-3p to the 3'-UTR of both mRNAs. MiR-548x-3p was overexpressed in osteoblasts-like cell lines decreasing the levels of MAFB and STAT1 mRNA and protein. We found that miR-548x-3p overexpression inhibits the proliferation, migration and invasion of the cell lines evaluated. Our results identified, by the first time, the potential role of miR-548x-3p as a modulator of the bone remodelling process by regulating the expression of MAFB and STAT1.

Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive and lethal disease, whose pathogenesis is associated with fibroblasts/myofibroblasts foci that produce excessive extracellular matrix accumulation in lung parenchyma. Hypoxia has been described as a determinant factor in its development and progression. However, the role of distinct members of this pathway is not completely described. METHODS: By western blot, quantitative PCR, Immunohistochemistry and Immunocitochemistry were evaluated, the expression HIF alpha subunit isoforms 1, 2 & 3 as well, as their role in myofibroblast differentiation in lung tissue and fibroblast cell lines derived from IPF patients. RESULTS: Hypoxia signaling pathway was found very active in lungs and fibroblasts from IPF patients, as demonstrated by the abundance of alpha subunits 1 and 2, which further correlated with the increased expression of myofibroblast marker αSMA. In contrast, HIF-3α showed reduced expression associated with its promoter hypermethylation. CONCLUSIONS: This study lends further support to the involvement of hypoxia in the pathogenesis of IPF, and poses HIF-3α expression as a potential negative regulator of these phenomena.

Influence of Genetic and Non-Genetic Risk Factors for Serum Uric Acid Levels and Hyperuricemia in Mexicans.

Risk of hyperuricemia is modified by genetic and environmental factors. Our aim was to identify factors associated with serum uric acid levels and hyperuricemia in Mexicans. A pilot Genome-wide association study GWAS was performed in a subgroup of participants (n = 411) from the Health Workers Cohort Study (HWCS). Single nucleotide polymorphisms (SNPs) associated with serum uric acid levels were validated in all the HWCS participants (n = 1939) and replicated in independent children (n = 1080) and adult (n = 1073) case-control studies. The meta-analysis of the whole HWCS and replication samples identified three SLC2A9 SNPs: rs1014290 (p = 2.3 × 10-64), rs3775948 (p = 8.2 × 10-64) and rs11722228 (p = 1.1 × 10-17); and an ABCG2 missense SNP, rs2231142 (p = 1.0 × 10-18). Among the non-genetic factors identified, the visceral adiposity index, smoking, the metabolic syndrome and its components (waist circumference, blood pressure, glucose and hyperlipidemia) were associated with increased serum uric acid levels and hyperuricemia (p < 0.05). Among the female HWCS participants, the odds ratio for hyperuricemia was 1.24 (95% CI, 1.01-1.53) per unit increase in soft drink consumption. As reported in other studies, our findings indicate that diet, adiposity and genetic variation contribute to the elevated prevalence of hyperuricemia in Mexico.

The Non-Aromatic Δ5-Androstenediol Derivative of Dehydroepiandrosterone Acts as an Estrogen Agonist in Neonatal Rat Osteoblasts through an Estrogen Receptor α-related Mechanism.

Purpose: It has been proposed that DHEA influences bone formation through, bioconversion to 17ß-estradiol; however, DHEA is converted to Δ5-androstenediol (Δ5-Adiol), a metabolite with estrogenic potential involved in diverse biological process. To gain new insight into the role of Δ5-Adiol in bone cells, we examined DHEA and Δ5-Adiol effects in neonatal rat and human hFOB1.19 osteoblasts. Methods: Osteoblast activity was assessed by analyzing proliferation, alkaline phosphatase activity, and expression of OSX and ALPL. We also examined binding affinities for osteoblast-ER and transcriptional activation of human (h)ERα, hERß or hAR in U2-OS cells. Results: The most striking finding was that Δ5-Adiol had greater stimulatory effect than DHEA on rat osteoblast proliferation and differentiation, as well as ALPL expression in human osteoblasts. Interestingly, the Δ5-Adiol or DHEA-induced effects were not precluded with letrozole or trilostane, consistent with bioconversion of DHEA to Δ5-Adiol due to elevated expression of Hsd17b1 in neonatal rat osteoblasts, suggesting a high level of 17ß-hydroxysteroid dehydrogenase type 1 activity. Conversely, Δ5-Adiol and DHEA-induced proliferative effects were inhibited with ICI 182780 alone or combined with trilostane, which correlates with the higher binding affinity of Δ5-Adiol for ER compared to DHEA. Furthermore, Δ5-Adiol showed a greater relative agonist activity for hERα than for hERß or hAR. Conclusion: This study is the first to show that a bioactive DHEA derivative stimulates E2-dependent osteoblast activities, including proliferation and differentiation in rat and human osteoblasts, through ERα-related mechanisms.

Polimorfismos de los genes JAG1, MEF2C y BDNF asociados con la densidad mineral ósea en mujeres del norte de México / JAG1, MEF2C and BDNF polymorphisms associated with bone mineral density in women from Northern México

Resumen Introducción. La osteoporosis se caracteriza por una baja densidad mineral ósea; la composición genética es uno de los factores que más influyen en ella, pero hay pocos estudios de genes asociados con esta condición en la población mexicana. Objetivo. Investigar la posible asociación de ocho polimorfismos de un solo nucleótido (Single Nucleotide Polymorphism, SNP) de los genes JAG1, MEF2C y BDNF con la densidad mineral ósea en mujeres del norte de México. Materiales y métodos. Participaron 124 mujeres de 40 a 80 años, sin parentesco entre ellas. Su densidad mineral ósea se determinó mediante absorciometría dual de rayos X y la genotipificación se hizo utilizando discriminación alélica mediante PCR en tiempo real; se estudiaron cuatro de los SNP del gen JAG1 (rs6514116, rs2273061, rs2235811 y rs6040061), tres del MEF2C (rs1366594, rs12521522 y rs11951031) y uno del BDNF (rs6265). El análisis estadístico de los datos obtenidos se hizo por regresión lineal. Resultados. El SNP rs2235811 presentó asociación significativa con la densidad mineral ósea de todo el cuerpo bajo el modelo de herencia dominante (p=0,024) y, aunque los otros SNP no tuvieron relación significativa con esta densidad, en ninguno de los modelos de herencia estudiados, se observó una tendencia hacia esta asociación. Conclusión. Los resultados sugieren que el SNP rs2235811 del gen JAG1 podría contribuir a la variación en la densidad mineral ósea de las mujeres del norte de México.

Abstract Introduction: Osteoporosis is characterized by a low bone mineral density. Genetic composition is one of the most influential factors in determining bone mineral density (BMD). There are few studies on genes associated with BMD in the Mexican population. Objective: To investigate the association of eight single nucleotide polymorphisms (SNP) of JAG1, MEF2C and BDNF genes with BMD in women of Northern México. Materials and methods: This study involved 124 unrelated Mexican women between 40 and 80 years old. BMD was determined by dual X-ray absorptiometry. Genotyping was performed using allelic discrimination by real time PCR. We analyzed the SNP of JAG1 (rs6514116, rs2273061, rs2235811 and rs6040061), MEF2C (rs1366594, rs12521522 and rs11951031), and BDNF (rs6265) and the data using linear regression. Results: The JAG1 SNP rs2235811 was associated with the BMD of the total body under the dominant inheritance model (p=0,024). Although the other SNPs were not associated with BMD in any of the inheritance models studied, a trend was observed. Conclusion: Our results suggest that the SNP rs2235811 in the JAG1 gene might contribute to the variation in BMD in women from northern México.

Circulating miR-215-5p and miR-642a-5p as potential biomarker for diagnosis of osteosarcoma in Mexican population.

Osteosarcoma is the most common malignant bone neoplasia affecting individuals in the second decade of life. The survival rate has not been improved during the last 25 years, in part because of the lack of specific markers. The microRNAs have been identified as important regulators of gene expression, experimental evidence suggests these molecules as key players in cancer development and progression. To identify miRNAs differentially expressed in serum from patients with osteosarcoma compared to healthy donors in Mexican population. Fifteen osteosarcoma patients and fifteen age and sex matched healthy individuals were recruited. Two pools of total RNA extracted from serum per study group were prepared and the miRNA expression profiles were analyzed through TaqMan Low Density Arrays. Validation was carried out through RT-qPCR using individual TaqMan assays for those miRNAs differentially expressed. Fifteen miRNAs were differentially expressed in osteosarcoma patients compared to healthy controls. Overexpression of miR-215-5p and miR-642a-5p was confirmed by validation through RT-qPCR. The expression analysis of miRNAs from serum in osteosarcoma patients revealed differential expression of miR-215-5p and miR-642a-5p. Both microRNAs are potential markers for osteosarcoma diagnosis.

The T>A (rs11646213) gene polymorphism of cadherin-13 (CDH13) gene is associated with decreased risk of developing hypertension in Mexican population.

Hypertension is a major public health problem affecting about 30% of the adult population and is associated with an increased risk of developing metabolic and cardiovascular disease. Recent reports have shown that the T-cadherin receptor characteristically expressed on endothelial and vascular smooth muscle cells is involved in hypertension. The aim of the present study was to evaluate the role of cadherin-13 (CDH13) gene polymorphisms as susceptibility markers for hypertension in Mexican population. Six CDH13 polymorphisms (rs11646213, rs11646411, rs6563943, rs3096277, rs3784990 and rs254340) were genotyped by 5' exonuclease TaqMan assays in a group of 644 hypertensive and 765 non-hypertensive individuals. Under co-dominant, recessive, and additive models, the CDH13 T>A (rs11646213) polymorphism was associated with decreased risk of developing hypertension when compared to non-hypertensive individuals (OR=0.61, 95% CI: 0.42-0.89, Pco-dom=0.019; OR=0.63, 95% CI: 0.46-0.87, Pres=0.005; OR=0.80, 95% CI: 0.66-0.96, Padd=0.016, respectively). All models were adjusted by gender, age, body index mass, type II diabetes mellitus, alcohol consumption, dyslipidemia and smoking habit. Linkage disequilibrium analysis showed one haplotype (TCACGG) with decreased frequency in hypertensive when compared to non-hypertensive individuals (OR=0.52, 95% CI: 0.33-0.82, P=0.0053). In summary, our data suggests that the CDH13 T>A (rs11646213) polymorphism is associated with decreased risk of developing hypertension in the Mexican population. In addition, it was possible to distinguish one haplotype associated with decreased risk and two for increased risk of develop hypertension.

Health workers cohort study: methods and study design / Cohorte de trabajadores de la salud: métodos y diseño del estudio

Abstract: Objective: To examine different health outcomes that are associated with specific lifestyle and genetic factors. Materials and methods: From March 2004 to April 2006, a sample of employees from three different health and academic institutions, as well as their family members, were enrolled in the study after providing informed consent. At baseline and follow-up (2010-2013), participants completed a self-administered questionnaire, a physical examination, and provided blood samples. Results: A total of 10 729 participants aged 6 to 94 years were recruited at baseline. Of these, 70% were females, and 50% were from the Mexican Social Security Institute. Nearly 42% of the adults in the sample were overweight, while 20% were obese. Conclusion: Our study can offer new insights into disease mechanisms and prevention through the analysis of risk factor information in a large sample of Mexicans.

Resumen: Objetivo: Examinar diferentes desenlaces en salud y su asociación con factores genéticos y del estilo de vida. Material y métodos: De marzo de 2004 a abril de 2006, una muestra de empleados de tres diferentes instituciones de salud y académicas, así como miembros de sus familias, fueron enrolados en el estudio, previa firma de consentimiento informado. Durante la medición basal y el seguimiento (2010-2013) los participantes completaron un cuestionario autoaplicado, exámenes físicos y proporcionaron muestras sanguíneas. Resultados: Fueron incluidos participantes (10 729) de entre 6 y 94 años en la medición basal. De estos, 70% fueron mujeres y 50% del Instituto Mexicano del Seguro Social. Aproximadamente 42% de los adultos tuvieron sobrepeso y 20% obesidad. Conclusión: Este estudio puede ofrecer conocimientos sobre los mecanismos de la enfermedad a través del análisis de factores de riesgo en una muestra de mexicanos.