Evaluation of DNA damage in obese children using the chromatin dispersion test.

Childhood obesity predicts adult obesity and may increase the lifetime risk of adverse health outcomes. Obesity is characterized by oxidative stress that can induce DNA damage; however, studies of childhood and adolescent obesity are scarce. We investigated DNA damage due to obesity in Mexican children using the chromatin dispersion test (CDT). We evaluated DNA damage to peripheral lymphocytes of 32 children grouped according to body mass index as normal weight (controls), overweight and obese groups using guidelines from the Centers for Disease Control (CDC). We found that the greatest DNA damage occurred in cells of obese children compared to normal weight and overweight children. Our findings support preventive action to obviate adverse health outcomes due to obesity.

Risk Association of TOX3 and MMP7 Gene Polymorphisms with Sporadic Breast Cancer in Mexican Women.

Breast cancer (BC) has one of the highest incidences and mortality worldwide. Single nucleotide polymorphisms (SNPs) in TOX3 rs3803662 and MMP7 rs1943779 have been associated with susceptibility to BC. In this case-control study, we evaluated the association of rs3803662 (TOX3)/rs1943779 (MMP7) SNPs with clinical features, immunohistochemical reactivity, and risk association with BC in women from northeastern Mexico. We compared 212 BC cases and 212 controls. DNA was isolated from peripheral blood to perform the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We calculated genotype frequencies, odds ratios, and 95% confidence intervals. We found that CT (Cytocine-Thymine) and TT (Thymine -Thymine) genotypes, and T alleles of TOX3 rs3803662, were associated with BC risk (p = 0.034, p = 0.011, respectively). SNP TOX3 rs3803662 was associated with positive progesterone receptors (PR) and triple-negative BC (TNBC) but not with estrogen receptor (ER) or HER2 reactivity. CT and TT genotypes (p = 0.006) and T alleles (p = 0.002) of SNP MMP7 rs1943779 were associated with risk of BC. We found that T alleles of TOX3 rs3803662 and MMP7 rs1943779 SNPs are associated with BC risk. These findings contribute to personalized medicine in Mexican women.

The Mitochondrial DNA Landscape of Modern Mexico.

Mexico is a rich source for anthropological and population genetic studies with high diversity in ethnic and linguistic groups. The country witnessed the rise and fall of major civilizations, including the Maya and Aztec, but resulting from European colonization, the population landscape has dramatically changed. Today, the majority of Mexicans do not identify themselves as Indigenous but as admixed, and appear to have very little in common with their pre-Columbian predecessors. However, when the maternally inherited mitochondrial (mt)DNA is investigated in the modern Mexican population, this is not the case. Control region sequences of 2021 samples deriving from all over the country revealed an overwhelming Indigenous American legacy, with almost 90% of mtDNAs belonging to the four major pan-American haplogroups A2, B2, C1, and D1. This finding supports a very low European contribution to the Mexican gene pool by female colonizers and confirms the effectiveness of employing uniparental markers as a tool to reconstruct a country's history. In addition, the distinct frequency and dispersal patterns of Indigenous American and West Eurasian clades highlight the benefit such large and country-wide databases provide for studying the impact of colonialism from a female perspective and population stratification. The importance of geographical database subsets not only for forensic application is clearly demonstrated.

The Convoluted Tubules of the Nephron Must Be Considered Elliptical, and Not Circular, in Stereological Studies of the Kidney.

INTRODUCTION: The diameter and area of the proximal convoluted tubule (PCT) and the distal convoluted tubule (DCT) are of the main parameters analyzed in stereological studies of the kidney. However, there is no consensus about if the PCT and DCT should be considered circular or elliptical in shape. OBJECTIVE: To analyze if there are significant differences in the diameter and area of the PCT and DCT, depending on whether they are considered circular or elliptical. METHODS: Paraffin-embedded sections of kidneys from CD1 mice were stained with hematoxylin and eosin and examined using a light microscope. Images were captured using a camera linked to image analysis software. A short diameter (d) and a long diameter (D) were measured in both PCT and DCT. A small circular area (SCA), a large circular area (LCA), and an elliptical area (EA) were calculated with mathematical formulas that incorporate d and D values, while a program area (PA) was provided by the software. RESULTS: There was a significant difference between d and D in both PCT (F = 1.354, Sig = 0.000) and DCT (F = 4.989, Sig = 0.000). Also, there were significant differences in the tubular areas in both PCT (F = 34.843, Sig = 0.000) and DCT (F = 22.390, Sig = 0.000); circular areas were different from elliptical areas (SCA and LCA vs. EA and PA). CONCLUSION: The convoluted tubules of the nephron must not be considered circular, but rather elliptical; care should be taken every time the tubules are analyzed in stereological studies of the kidney, especially when evaluating their diameters and areas.

Quick assessment of DNA damage in cervical epithelial cells using a chromatin dispersion test.

PURPOSE: This study was aimed to quantify genomic DNA breakages in the cervical epithelium cells of patients diagnosed with different grades of cervical lesions using a quick test based on chromatin dispersion after controlled protein depletion. The association between the progressive stages of cervical dysplasia and the levels of DNA damage, taking into account the presence of papillomavirus human (HPV) infection, was investigated. METHODS: A hospital-based unmatched case-control study was conducted during 2018 with a sample of 78 women grouped according to histological diagnosis as follows: 23 women with low grade-squamous intraepithelial lesion (LG-SIL), 34 women with high grade- squamous intraepithelial lesion (HG-SIL), and three women with cervical carcinoma (CC). In parallel, 15 women without cervical lesions were included as a Control cohort. DNA damage levels in cervical epithelial cells were assessed using the chromatin dispersion test (CDT) and controlled in parallel with DNA breakage detection coupled with florescent in situ hybridization (DBD‒FISH) using whole genomic DNA probes. RESULTS: CDT produces different morphotypes in the cervical epithelium that can be associated with the level of DNA breakage revealed with DBD‒FISH. A significant increase of DNA damage was correlated with the histological progression of the patients and human papillomavirus (HPV) infection. CONCLUSION: The CDT is a simple, accurate and inexpensive morphological bioassay to identify different levels DNA damage that can be associated with the level of abnormal cells present in the cervical epithelium in patients who commonly present HPV infection.

DBD-FISH, an effective marker for detecting genotoxicity in buccal mucosa exfoliated cells of patients with oral cancer.

Oral squamous cell carcinoma (OSCC) is characterized by increased genetic instability as an essential variable of event of neoplastic transformation. The aim of this study was to evaluate genomic instability in exfoliated cells from the buccal mucosa of patients with OSCC vs. the control group, using DNA Breakage Detection/Fluorescence In Situ hybridization (DBD-FISH). Exfoliated cells from the buccal mucosa were obtained from 38 patients with oral cancer (case group) and from 10 individuals without oral lesions (control group). DNA damage was evaluated by DBD-FISH using the whole-genome DNA probe and digital imaging analysis. Collaterally, HPV infection was determined utilizing the INNO-LiPA HPV kit. Patients with OSCC showed an increase in the hybridization signal five times more intense than that of the baseline level of DNA damage detected in control individuals. The best cutoff value for predicting oral squamous cell carcinoma was 67.46, and an Odds Ratio (OR) value of 87. HPV detection analysis revealed than one patient with OSCC (2.6%) was positive for HPV. All controls were negative HPV. In conclusion, DBD-FISH permitted the clear visualization of level high of DNA damage in the buccal epithelial cells of patients with OSSC respect to control group. Chromosome instability in oral mucosa may be an individual marker of malignant transformation in OSCC.

ADIPOQ single nucleotide polymorphisms and breast cancer in northeastern Mexican women.

BACKGROUND: Adiponectin gene (ADIPOQ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) of ADIPOQ in Mexican women with BC and to determine if they show an association with it. METHODS: DNA samples from 397 patients and 355 controls were tested for the ADIPOQ gene SNPs: rs2241766 (GT) and rs1501299 (GT) by TaqMan allelic discrimination assay. Hardy-Weinberg equilibrium (HWE) was tested. Multiple SNP inheritance models adjusted by age and body mass index (BMI) were examined for the SNP rs1501299. RESULTS: We found that in the frequency analysis of rs1501299 without adjusting the BMI and age, the genotype distribution had a statistically significant difference (P = 0.003). The T allele was associated with a BC risk (OR, 1.99; 95% CI 1.13-3.51, TT vs. GG; OR, 1.53; 95% CI 1.12-2.09, GT vs. GG). The SNP rs2241766 was in HW disequilibrium in controls. In conclusion, the rs1501299 polymorphism is associated with a BC risk. CONCLUSIONS: Identification of the genotype of these polymorphisms in patients with BC can contribute to integrate the risk profile in both patients and their relatives as part of a comprehensive approach and increasingly more personalized medicine.

Asociación de horas de sueño y adiposidad en niños y adolescentes del noreste de México / Association of sleep duration and adiposity in children and adolescents in northeastern Mexico

FUNDAMENTOS: Se ha identificado que el sueño es un factor de riesgo de adiposidad en la población pediátrica que procede de países de altos ingresos económicos. El objetivo de este estudio fue determinar la asociación entre horas de sueño nocturno y adiposidad mediante índice de masa corporal (IMC) y perímetro de cuello (PC) en niños y adolescentes del noreste de México, país de ingresos medios. MÉTODOS: Se realizó un análisis de regresión logística a partir de 746 escolares de 4 a 18 años de edad y se estimaron las tasas de posibilidad de riesgo de obesidad según IMC y PC frente a horas de sueño entre semana y fines de semana. RESULTADOS: El promedio de horas de sueño nocturno en preescolares fueron 9,1 (±1,2), en escolares 8,3 (±1,2) y adolescentes 6,21 (±1,0). Los factores asociados a adiposidad mediante PC fueron horas de sueño entre semana, edad, sexo masculino y roncar; para adiposidad por IMC fueron sexo masculino y roncar (p < 0,05). CONCLUSIONES: Existe asociación entre adiposidad del cuello con horas de sueño en días entre semana, no así con adiposidad mediante IMC. La medición del PC puede ser un enfoque innovador para determinar adiposidad y para intervenciones de prevención que ayuden a garantizar la duración adecuada del sueño en la población pediátrica

BACKGROUND: It has been identified that sleep is risk factor adiposity in the pediatric population who come from high income countries. The objective of this study was to determine the association between hours of nighttime sleep and adiposity using body mass index (BMI) and neck circumference (NC) in children and adolescents in northeastern Mexico, middle-income country. METHODS: A logistic regression analysis was carried out from 746 schoolchildren aged from 4 to 18 years and the obesity risk possibility rates by BMI and PC were estimated against sleep hours during the week and weekends. RESULTS: The average hours of nighttime sleep in preschoolers were 9.1 (±1.2), in schoolchildren 8.3 (±1.2) and adolescents 6.21 (±1.0). The factors associated with adiposity by NC were hours of sleep during the week, age, male sex and snoring; the factors for adiposity by BMI were male sex and snoring (p <0.05). CONCLUSIONS: There is an association between adiposity of the neck with hours of sleep on weekdays, but not with adiposity by to BMI. NC measurement can be an innovative approach to determine adiposity andfor prevention interventions that help ensure adequate sleep duration in the pediatric population

Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women.

Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.

Whole exome sequencing identifies multiple novel candidate genes in familial gastroschisis.

BACKGROUND: Genetic association studies for gastroschisis have highlighted several candidate variants. However, genetic basis in gastroschisis from noninvestigated heritable factors could provide new insights into the human biology for this birth defect. We aim to identify novel gastroschisis susceptibility variants by employing whole exome sequencing (WES) in a Mexican family with recurrence of gastroschisis. METHODS: We employed WES in two affected half-sisters with gastroschisis, mother, and father of the proband. Additionally, functional bioinformatics analysis was based on SVS-PhoRank and Ensembl-Variant Effect Predictor. The latter assessed the potentially deleterious effects (high, moderate, low, or modifier impact) from exome variants based on SIFT, PolyPhen, dbNSFP, Condel, LoFtool, MaxEntScan, and BLOSUM62 algorithms. The analysis was based on the Human Genome annotation, GRCh37/hg19. Candidate genes were prioritized and manually curated based on significant phenotypic relevance (SVS-PhoRank) and functional properties (Ensembl-Variant Effect Predictor). Functional enrichment analysis was performed using ToppGene Suite, including a manual curation of significant Gene Ontology (GO) biological processes from functional similarity analysis of candidate genes. RESULTS: No single gene-disrupting variant was identified. Instead, 428 heterozygous variations were identified for which SPATA17, PDE4DIP, CFAP65, ALPP, ZNF717, OR4C3, MAP2K3, TLR8, and UBE2NL were predicted as high impact in both cases, mother, and father of the proband. PLOD1, COL6A3, FGFRL1, HHIP, SGCD, RAPGEF1, PKD1, ZFHX3, BCAS3, EVPL, CEACAM5, and KLK14 were segregated among both cases and mother. Multiple interacting background modifiers may regulate gastroschisis susceptibility. These candidate genes highlight a role for development of blood vessel, circulatory system, muscle structure, epithelium, and epidermis, regulation of cell junction assembly, biological/cell adhesion, detection/response to endogenous stimulus, regulation of cytokine biosynthetic process, response to growth factor, postreplication repair/protein K63-linked ubiquitination, protein-containing complex assembly, and regulation of transcription DNA-templated. CONCLUSION: Considering the likely gene-disrupting prediction results and similar biological pattern of mechanisms, we propose a joint "multifactorial model" in gastroschisis pathogenesis.

Genetic Variants at the rs4720169 Locus of TBX20 and the rs12921862 Locus of AXIN1 May Increase the Risk of Congenital Heart Defects in the Mexican Population: A Pilot Study.

Background: Congenital heart defects (CHDs) are the most common type of birth defects and a major cause of infant mortality. Although knowledge of genetic risk variants for CHDs is scarce, most cases of CHDs are considered to be due to multifactorial inheritance. Objective: To analyze the association of 14 single nucleotide polymorphic variants previously associated with a risk of CHDs in a Mexican population with isolated CHDs. Materials and Methods: DNA samples obtained from healthy subjects and from subjects with isolated atrial, ventricular, or atrioventricular septal defects living in Northeastern Mexico were analyzed by real time-polymerase chain reaction for allelic discrimination of genetic variants of the genes TBX1, TBX20, ASTX-18-AS1, AXIN1, MTHFR, NKX2.5, BMP4, and NFATc1. The odds ratios (ORs) for allele and genotype frequencies and inheritance models were obtained. Results: Forty-two patients and 138 controls were included. Two variants were found to confer a risk of CHDs: variant rs4720169 of TBX20 in which the OR for the heterozygous state was 1.88 (95% confidence interval [CI]: 1.12-3.14, p = 0.010), whereas the OR for the homozygous state was 3.82 (95% CI: 1.18-12.3, p = 0.010); and variant rs12921862 of AXIN1 in which the OR for the heterozygous state was 4.15 (95% CI: 2.42-7.10; p ≤ 0.001), whereas the OR for the homozygous state was 9.2 (95% CI: 1.31-64.7, p = 0.008) for allele A. Conclusion: Genetic variants of the TBX20 and AXIN1 genes confer a significantly increased risk of congenital septal heart defects in a population from Northeastern Mexico.

Morphometric analysis of the non-epithelial areas of mouse bronchioles through the normal aging process.

Aging is associated with changes in the structure and function of the lung that may increase susceptibility to chronic lung diseases. The aim of this study was the morphometric assessment of the non-epithelial areas of the bronchioles of mouse through the normal aging process. Lungs from CD1 mice at the age of 2, 6, 12, 18, or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Sections were cut, stained with Masson trichrome, and examined using a light microscope. High-resolution color images were captured using a camera linked to image analysis software to measure areas and lengths. We observed in the bronchioles through the aging process an increase of the total area, an increase of the lumen area, and a decrease of the wall area. In conclusion, our results revealed structural changes in the bronchioles of mouse through the normal aging process. These alterations are likely to contribute to development of chronic lung diseases.

Bioinformatic Analysis of Gene Variants from Gastroschisis Recurrence Identifies Multiple Novel Pathogenetic Pathways: Implication for the Closure of the Ventral Body Wall.

We investigated whether likely pathogenic variants co-segregating with gastroschisis through a family-based approach using bioinformatic analyses were implicated in body wall closure. Gene Ontology (GO)/Panther functional enrichment and protein-protein interaction analysis by String identified several biological networks of highly connected genes in UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, AOX1, NOTCH1, HIST1H2BB, RPS3, THBS1, ADCY9, and FGFR4. SVS-PhoRank identified a dominant model in OR10G4 (also as heterozygous de novo), ITIH3, PLEKHG4B, SLC9A3, ITGA2, AOX1, and ALPP, including a recessive model in UGT1A7, UGT1A6, PER2, PTPRD, and UGT1A3. A heterozygous compound model was observed in CDYL, KDM5A, RASGRP1, MYBPC2, PDE4DIP, F5, OBSCN, and UGT1A. These genes were implicated in pathogenetic pathways involving the following GO related categories: xenobiotic, regulation of metabolic process, regulation of cell adhesion, regulation of gene expression, inflammatory response, regulation of vascular development, keratinization, left-right symmetry, epigenetic, ubiquitination, and regulation of protein synthesis. Multiple background modifiers interacting with disease-relevant pathways may regulate gastroschisis susceptibility. Based in our findings and considering the plausibility of the biological pattern of mechanisms and gene network modeling, we suggest that the gastroschisis developmental process may be the consequence of several well-orchestrated biological and molecular mechanisms which could be interacting with gastroschisis predispositions within the first ten weeks of development.

Pediatric pituitary adenomas in Northeast Mexico. A follow-up study.

PURPOSE: To review incidence, treatment and outcome of pediatric pituitary adenomas (PAs). METHODS: A follow-up study patients with the age of ≤19 years old who were treated from 1995 to 2015 in Mexico. RESULTS: Out of 1244 diagnosed PA, 43 patients were children (35 females, 8 males) with a mean age of 17.2 years. The majority were macroadenomas (70%) with prolactinomas (PRL) dominating (63%) followed by non-functioning adenomas (21%). In total, 40% were diagnosed as invasive. Growth hormone (GH) secreting adenomas, adrenocorticotropic hormone secreting and mixed GH-PRL secreting were rare. The treatment modalities were dopamine agonists and surgery. The average treatment time was 44 months with an average follow-up period of 104 months. Sixty-eight percent (27/40) of the patients had complete response after long time follow-up. Thirty-one percent did not respond to treatment whereof three patients died due to advanced disease and late intervention. The principal causes for treatment failure were treatment resistance, late intervention and poor patient compliance. CONCLUSIONS: Sixty eight percent had complete treatment response without any sign of disease, while ~31% did not respond to treatment or did not comply to follow up/treatment. Optimized early diagnose, treatment methods with early intervention, long time follow-up and with better measures for patient compliance should improve outcomes.

A clinical-pathogenetic approach on associated anomalies and chromosomal defects supports novel candidate critical regions and genes for gastroschisis.

BACKGROUND: Gastroschisis has been assumed to have a low rate of syndromic and primary malformations. We aimed to systematically review and explore the frequency and type of malformations/chromosomal syndromes and to identify significant biological/genetic roles in gastroschisis. METHODS: Population-based, gastroschisis-associated anomalies/chromosomal defects published 1950-2018 (PubMed/MEDLINE) were independently searched by two reviewers. Associated anomalies/chromosomal defects and selected clinical characteristics were subdivided and pooled by race, system/region, isolated, and associated cases (descriptive analysis and chi-square test were performed). Critical regions/genes from representative chromosomal syndromes including an enrichment analysis using Gene Ontology Consortium/Panther Classification System databases were explored. Fisher's exact test with False Discovery Rate multiple test correction was performed. RESULTS: Sixty-eight articles and 18525 cases as a base were identified (prevalence of 17.9 and 3% for associated anomalies/chromosomal defects, respectively). There were 3596 associated anomalies, prevailing those cardiovascular (23.3%) and digestive (20.3%). Co-occurring anomalies were associated with male, female, American Indian, Caucasian, prenatally diagnosed, chromosomal defects, and mortality (P < 0.00001). Gene clusters on 21q22.11 and 21q22.3 (KRTAP), 18q21.33 (SERPINB), 18q22.1 (CDH7, CDH19), 13q12.3 (FLT1), 13q22.1 (KLF5), 13q22.3 (EDNRB), and 13q34 (COL4A1, COL4A2, F7, F10) were significantly related to biological processes: blood pressure regulation and/or vessel integrity, angiogenesis, coagulation, cell-cell and/or cell-matrix adhesion, dermis integrity, and wound healing (P < 0.05). CONCLUSIONS: Our findings suggest that gastroschisis may result from the interaction of several chromosomal regions in an additive manner as a pool of candidate genes were identified from critical regions supporting a role for vascular disruption, thrombosis, and mesodermal deficiency in the pathogenesis of gastroschisis.

Description of Genetic Variants in BRCA Genes in Mexican Patients with Ovarian Cancer: A First Step towards Implementing Personalized Medicine.

Gynecologic cancers are among the leading causes of death worldwide, ovarian cancer being the one with the highest mortality rate. Olaparib is a targeted therapy used in patients presenting mutations in BRCA1 and BRCA2 genes. The aim of this study was to describe BRCA1 and BRCA2 gene variants in Mexican patients with ovarian cancer. Sequencing of BRCA1 and BRCA2 genes from tumors of 50 Mexican patients with ovarian cancer was made in a retrospective, non-randomized, and exploratory study. We found genetic variants in 48 of 50 cases. A total of 76 polymorphic variants were found in BRCA1, of which 50 (66%) had not been previously reported. Furthermore, 104 polymorphic variants were found in BRCA2, of which 63 (60%) had not been reported previously. Of these polymorphisms, 5/76 (6.6%) and 4/104 (3.8%) were classified as pathogenic in BRCA1 and BRCA2, respectively. We have described the genetic variants in BRCA1 and BRCA2 of tumors from Northeast Mexican patients with sporadic ovarian cancers. Our results showed that the use of genetic testing helps recognize patients that carry pathogenic variants which could be beneficial for personalized medicine treatments.

The RANKL rs12585014 polymorphism is associated with age at menarche in postmenopausal women with hip fracture.

The RANK/RANKL/OPG signaling is important in the regulation of bone turnover. The aim of the present work was to analyze the rs3018362 and rs12585014 polymorphisms in the RANK and RANKL genes, as well as risk factors in postmenopausal women. Women with hip fracture, with femoral neck osteoporosis and controls (n = 646) were recruited. From these, 303 women who fulfill the inclusion criteria were genotyped using real-time PCR with TaqMan probes. There were no associations of the rs3018362 and rs12585014 with osteoporosis or fracture. When women were divided by age at menarche, the rs12585014 GG genotype was strongly associated with age at menarche >13 years [p = .00774, OR = 6.429 (1.907-21.103)] in women with hip fracture. Significant differences in risk factors such as body mass index, age at menopause, use of estrogens, the presence of hypertension, and diabetes mellitus were found. Carrying the GG genotype of rs12585014 entails a higher risk of having menarche later (>13 years), which could involves a greater risk of fractures. The rs3018362 and rs12585014 do not seem to be associated with hip osteoporosis or hip fracture in Mexican women.

The phenotype, psychotype and genotype of bruxism.

Bruxism is a jaw muscle activity that involves physio-pathological, psycho-social, hereditary and genetic factors. The purpose of this study was to determine the associations between self-reported bruxism, anxiety, and neuroticism personality trait with the rs6313 polymorphism in the gene HTR2A. A sample of 171 subjects of both sexes (14-53 years of age) was included. The control group (group 1, n=60) exhibited no signs or symptoms of bruxism. The case group had signs and symptoms of bruxism (n=112) and was subdivided into group 2, bruxism during sleep (n=22); group 3, awake bruxism (n=44); and group 4 combined bruxism (n=46). As diagnostic tools, the Self-Reported Bruxism Questionnaire (SBQ), the Beck Anxiety Inventory (BAI) and the Eysenck Personality Questionnaire Revised-Abbreviated (EPQR-A) were used. HTR2A (rs6313) SNPs were determined by qPCR for all the participants. The packages SPSS, maxLik and EPI-INFO were used for data analysis. The combined bruxism group reported higher scores in bruxism symptoms, mean = 32.21; anxiety symptoms, mean = 14.80; and neuroticism, mean = 3.26. Combined bruxism was associated with a higher degree of neuroticism (OR=15.0; CI 1.52-148.32) and anxiety in grade 3-moderate (OR=3.56; CI 1.27-10.03), and grade 4-severe (OR=8.40; CI 1.45-48.61), as determined using EPISODE computer software. Genotypic homogeneity analysis revealed no significant differences in allele frequency (P=0.612) among the four groups. The population was in Hardy-Weinberg equilibrium (maxLik package). In conclusion, the three instruments confirm traits of bruxism, anxiety and neuroticism in individuals with bruxism. These data were ratified when the sample was divided by genotypic homogeneity. On the other hand, there was no significant difference between the groups in the SNPs rs6313 from the HTR2A gene.

Genetic variants conferring susceptibility to gastroschisis: a phenomenon restricted to the interaction with the environment?

BACKGROUND: Genes involved in gastroschisis have shown a strong interaction with environmental factors. However, less is known about its influence. We aimed to systematically review the genetic associations of gastroschisis, to summarize whether its genetic susceptibility has been restricted to the interaction with the environment, and to identify significant gaps that remain for consideration in future studies. METHODS: Genetic association studies of gastroschisis published 1980-2017 (PubMed/MEDLINE) were independently searched by two reviewers. Significant SNP-gastroschisis associations were grouped into crude and stratified risks, whereas SNPs were assessed from two or more independent studies. Frequencies, odds ratios, and 95% confidence intervals were pooled using descriptive analysis and Chi-square test accounting for heterogeneity. RESULTS: Seven eligible articles capturing associations of 14 SNPs from 10 genes for crude risk (including 10 and 4 SNPs with increased and decreased risk, respectively) and 30 SNPs from 14 genes for stratified risk in gastroschisis (including 37 and 14 SNPs with increased and decreased risk, respectively) were identified (Fisher's exact test, P = 0.438). The rs4961 (ADD1), rs5443 (GNB3), rs1042713, and rs1042714 (ADRB2) were significantly associated with gastroschisis. CONCLUSIONS: Genetic susceptibility in gastroschisis is not restricted to the interaction with the environment and should not be too narrowly focused on environmental factors. We found significant associations with four SNPs from three genes related to blood pressure regulation, which supports a significant role of vascular disruption in the pathogenesis of gastroschisis. Future studies considering gene-gene or gene-environmental interactions are warranted for better understanding the etiology of gastroschisis.

Prevalence, Mortality, and Spatial Distribution of Gastroschisis in Mexico.

STUDY OBJECTIVE: To explore the prevalence, mortality, and spatial distribution of gastroschisis using a large population-based sample with cases identified according to birth and death certificates (ICD-10 diagnosis code Q79.3, gastroschisis) through the General Directorate of Health Information of the Secretary Health of Mexico, over the course of a 15-year period. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A descriptive study examining 10,287 cases of gastroschisis was performed from 2000-2014 using public natality data for denominators (more than 25 million live births). Gastroschisis prevalence and mortality was calculated for each of year, state, maternal, and newborn characteristics. Spatial distribution was analyzed according to gastroschisis prevalence in the 32 states of Mexico. RESULTS: Gastroschisis prevalence was 4.01 per 10,000 live births (annual trend 2.09-6.85). Mortality associated with gastroschisis was 1.28 per 10,000 live births. Women younger than 20 years old, primiparae, and preterm infants had the highest gastroschisis-related prevalence (13.12, 5.83, and 7.51 per 10,000 live births, respectively). Gastroschisis prevalence and mortality did not differ according to newborn sex. A negative binomial distribution, variance (82,391.87) greater than the mean (321.47) was identified. CONCLUSION: Our findings show an increasing temporal trend for gastroschisis since 2000 in Mexico. Additionally, gastroschisis might follow in future instances a positive binomial or Poisson distribution. Therefore, improving surveillance of risk factors and supporting research for gastroschisis is warranted among maternal age younger than 25, particularly, younger than 20 years of age.