Mexican Cohort Research Articles

Overlapping presentations and diverse genetic defects characterize neuroendocrine neoplasms in a Mexican cohort.

Genetic tests are part of the routine clinical approach to syndromic and nonsyndromic phenotypes of neuroendocrine neoplasms (NENs). Current data on phenotype-genotype associations in NENs, however, do not accurately represent all populations. To describe the frequency, inventory, and clinical associations of germline defects associated with multiple types of NENs in a Mexican cohort. Blood DNA from Mexican adults with NENs was analyzed with a 53-gene NGS panel developed ad hoc (n=90) or Sanger sequencing (n=2). Single nucleotide variants, indels and structural variants were identified, classified, and subjected to orthogonal confirmation. When possible, tumor samples and blood DNA from additional family members were tested using Sanger sequencing. Ninety-two probands (70.7% women, 51.5% sporadic) were included; sixteen carried pathogenic or likely pathogenic (P/LP) variants and were significantly younger at disease onset, compared with the rest (29.6±10,7 vs. 40 [21.5-51.5] years, P=0.0384). Likely driving variants were identified in three-quarters of Von Hippel Lindau syndrome cases, one-third of multiple endocrine neoplasia type 1 (MEN1), one-quarter of early-onset acromegaly/gigantism, and individual cases of Cushing's disease, MEN2A, and medullary thyroid carcinoma. One patient with clinical MEN1 associated with an SDHA variant and one with a pituitary tumor and neurofibromatosis type 1 were also identified. Probands with familial disease were more likely to carry P/LP variants, compared with sporadic cases (26.7 vs 8.5%, P=0.0282). P/LP variants were identified in 17.4% of individuals with NENs. Our research provides a view of the landscape of NEN drivers in a population not previously characterized.

Association between methyl-CpG-binding domain protein 5 gene and depressive symptoms in Mexican population: Results from MxGDAR/Encodat cohort.

To explore the association between 75 candidate genes previously reported in subjects with anxiety symptoms (AS) and depressive symptoms (DS) in a Mexican cohort. The sample included 2012 individuals from the Mexican Genomic Database for Addiction Research (MxGDAR/Encodat) cohort, 198 showed AS, 266 DS, 66 anxiety and depressive symptoms (ADS), and 1482 healthy controls. The DI-PAD screening questionnaire was used to evaluate lifetime AS and DS. The sample was genotyped with the commercial microarray PsychArray BeadChip. We identified 707 SNPs of 75 genes previously associated with AS and DS. PLINK's logistic regression approach was performed. The analysis showed association between the rs2437092 (p=3.89x10-5) of LAMA and rs11066591 (p=4.06x10-5) of MYO1H with anxiety and depressive symptomatology. Additionally, rs7578002 (p=7.9x10-6) and rs1234428 (p=1.94x10-5) of MBD5 found association with DS. However, after adjustment for age, sex, and the three genetic principal components, only the association of rs7578002 (p=5.85x10-5) and rs1234428 (p=8.15x10-5) of MBD5 with DS remained. Our study replicated the association between MBD5 and DS. The MBD5 protein is involved in gene silencing, suggesting its potential implication in the development of DS in the Mexican population.

High Prevalence of Severe Depression in Mexican Patients Diagnosed with HIV Treated with Efavirenz and Atazanavir: Clinical Follow-Up at Four Weeks and Analysis of TPH2 SNPs.

Efavirenz (EFV) causes neuropsychiatric effects such as anxiety, depression, and suicidal thoughts in people with HIV (PWH). Depressive disorders have been associated with the Tryptophan hydroxylase type 2 (TPH2) gene. Objectives: This study determines the genotypes and allelic frequencies of three TPH2 single nucleotide polymorphisms (SNPs) in a Mexican cohort of HIV-1 treatment-naïve-patients and the severity of depressive symptoms at baseline and after a four-week clinical follow-up of antiretroviral treatment. Methods: In a pilot prospective study, eighty-one antiretroviral treatment-naïve patients were recruited from the Infectious Disease Hospital, National Medical Center "La Raza", in Mexico City. Of these, 39 were treated using a set-dose combination regimen of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus EFV and 42 were treated with TDF/FTC plus atazanavir/ritonavir (ATV/r), and fifty-nine control volunteers. Genomic DNA was obtained from peripheral blood mononuclear cells. All DNA samples underwent qPCR utilizing TaqMan probes for the three TPH2 SNPs studied. All participants underwent evaluation utilizing the Beck Depression Inventory. Results: Of the three SNPs examined, none exhibited any notable differences in the distribution of the alleles between the groups; nevertheless, rs4570625 TT and rs1386493 GG presented a twofold and fivefold greater risk of severe depression in PWH, respectively, independently of the treatment. Among PWH, those treated with EFV experienced severe depression at a higher rate of 90.4% after four weeks, compared to 87.5% in those treated with ATV/r. Conclusions: High rates of severe depression were identified in PWH, who presented the rs4570625 TT and rs1386493 GG polymorphic variants. Depression increased after four weeks of treatment and was higher with EFV than ATV/r. It is crucial to emphasize the necessity of conducting psychiatric monitoring for every patient with HIV and administering prompt antidepressant treatment.

Inadequate identification of high cardiovascular risk and carotid plaques in rheumatoid arthritis patients by the 2024 Predicting Risk of Cardiovascular EVENTs and the 2013 Atherosclerotic Cardiovascular Disease algorithms: findings from a Mexican cohort.

The American College of Cardiology/American Heart Association introduced the Predicting Risk of Cardiovascular EVENTs (PREVENT™) algorithm to estimate the 10-year risk of developing cardiovascular disease. We aimed to assess the cardiovascular risk (CVR) reclassification among rheumatoid arthritis (RA) patients using traditional CVR algorithms-the 2024 PREVENT™ and the 2013 Atherosclerotic Cardiovascular Disease (ASCVD)-and the presence of carotid plaque (CP). This was a cross-sectional study nested of a RA patients' cohort. A certified radiologist performed a high-resolution B-mode carotid ultrasound to identify the presence of CP. The CVR evaluation was performed by a cardiologist, blinded to carotid ultrasound results, using the PREVENT™ and the ASCVD algorithms. Cohen's kappa (k) coefficient assessed concordance between high-risk classification by CVR algorithms and CP presence. ROC curve analysis evaluated the algorithms' capacity to identify RA patients with CP. The cutoff point was determined by the Youden-Index, with p < 0.05 as statistically significant. A total of 210 RA patients were included. The reclassification of CVR due to CP was 34.3% for the PREVENT™ algorithm and 30.0% for the ASCVD algorithm. Of these, 44.4% and 71.4%, respectively, were initially classified as low risk. Concordance between CVR algorithms and carotid ultrasound showed slight agreement (k = 0.032 and k = 0.130, respectively). The PREVENT™ algorithm did not identify more than one-third of high-CVR RA patients with indication of starting statin therapy based on carotid ultrasound findings. The PREVENT™ and ASCVD algorithms showed poor performance in identifying RA patients with CP. Key Points • The presence of CP was identified in more than a third of the evaluated RA patients (35.7%), classifying them as high CVR. • CVR reclassification by the presence of CP was observed in 34.3% RA patients with the PREVENTTM algorithm and in 30.0% RA patients with the ASCVD algorithm. • Most of the reclassified patients belonged to the low-risk category, 44.4% with the PREVENTTM algorithm and 71.4% with the ASCVD algorithm. • When evaluating the concordance between the ASCVD algorithm and the carotid ultrasound for high-risk classification, a slight agreement was found (k = 0.130).

Evaluation of Type 2 diabetes mellitus, Alzheimer's disease, and olfactory dysfunction relationships

AbstractBackgroundType 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and insulin resistance. Historically, it is linked to greater cognitive decline and risk of Alzheimer's dementia. Although deregulations in the insulin signaling pathway have been identified, further investigation is needed. Diabetic patients over 60 years of age, in addition to facing cognitive risks, show olfactory deficits like AD. Neuronal precursors in the olfactory epithelium (hONE NPCs) offer a valuable model for studying the connection between T2DM and AD. Nasal exfoliates and plasma samples were collected from diabetic patients with or without cognitive decline and healthy controls. Assessment of biomarkers, the insulin signaling pathway and the posttranslational modification OGlacNac were done.MethodWe divided our study groups into apparently healthy subjects (AHS), subjects with cognitive impairment (SMCI), subjects with T2DM without cognitive impairment (ST2DM), and subjects with type 2 diabetes with cognitive impairment (ST2DM‐SMCI). We obtained hONE NPCs cell cultures from the volunteers through a non‐invasive nose exfoliate, those cells were characterized by WB and ICC. We obtained blood samples for the detection of HbA1c and AD biomarkers. We performed MoCA Test, medical interview and an olfactory test for each volunteer.ResultWe isolated and cultured human hONE NPCs from a Mexican cohort of 60 individuals over 50 years old diabetic and nondiabetic with or without MCI. We collected clinical data, performed MoCA test, and an olfactory test, collected blood samples, and evaluated glucose levels to search for possible correlations among these variables.Our results showed increased expression of IRS‐1 between control subjects (AHI) vs subjects with SMCI+ST2DM and a significant increase in OGlacNac of the IRS‐1 receptor between the control (AHI) group versus the SMCI and SMCI+ST2DM.ConclusionWe obtained a positive correlation between the olfactory and MoCA test and a non‐significant trend of negative correlation between the MoCA score and the HbA1c. A significant increase in IRS‐1 expression between AHI vs. subjects with SMCI+ST2DM was detected, and a significant increase in OGlacNac of the IRS‐1 receptor between the AHI versus the SMCI and SMCI+ST2DM. Thus, the hONE NPC cells constitute an accessible model to study the relationship between T2DM, AD, and olfactory dysfunction.

Low Antenatal Care Number of Consultations Is Associated with Gestational Weight Gain and Birth Weight of Offspring of Teenage Mothers: A Study Based on Colombian and Mexican Cohorts.

More than 70% of pregnant adolescents in developing countries experience inappropriate gestational weight gain (GWG). To determine the association of the number of antenatal care visits (ANC) with GWG, birth weight, and their differences between two countries. A prospective study was conducted in two cohorts of adolescents, one from Mexico and one from Colombia. The study calculated pregestational body mass index (BMI), obtained GWG and birth weight, and collected socioeconomic characteristics. Birth weight was categorized according to gestational age. A total of 690 mother-child pairs were included, of which 42.6% were Colombian and 57.4% Mexican. The study found no association between socioeconomic characteristics and GWG or birth weight. Colombian adolescents were more likely to experience insufficient GWG (68%), compared with 36% of Mexican adolescents. Colombian adolescents who attended fewer than eight ANC visits were at increased risk of insufficient GWG, whereas Mexican adolescents were at increased risk of excessive GWG. Mexican adolescents who began their pregnancies overweight or obese were at increased risk of excessive GWG. Fewer than eight ANC visits were associated with small for gestational age (SGA) in the Mexican cohort. Inadequate numbers of ANC visits were associated with excessive and insufficient GWG, and SGA. Promoting ANC in adolescent pregnancy is essential to prevent suboptimal GWG and SGA. This study highlights the need for interventions targeting pregnant adolescents from low socioeconomic backgrounds, prioritizing early initiation of prenatal care (first trimester) and a drastic reduction in the high rates of cesarean sections in this group.

Economic Disadvantage During Childhood, Obesity, and Diabetes Across Three Birth Cohorts of Older Mexicans.

Diabetes prevalence has increased markedly in Mexico. We examined the individual and joint contributions of economic disadvantage during childhood (EDDC) and elevated body weight on diabetes prevalence in 3 cohorts of Mexican adults. Data on those 60-69 years old from the 1930-1939, 1940-1949, and 1950-1959 birth cohorts in Waves 1 (2001), 3 (2012), and 5 (2018) of the Mexican Health and Aging Study were used. EDDC was defined as the absence of a toilet in the household before age 10. Body mass status was defined using self-reported perceived body image at age 50. Diabetes was based on respondent reports. Supplementary analyses using HbA1c as a criterion for diabetes were conducted. A regression-decomposition approach was implemented. Logistic regression models included adjustments for sociodemographic characteristics and access to medical care. Diabetes prevalence was 23% overall and 11%, 25%, and 26% in the 1930-1939, 1940-1949, and 1950-1959 cohorts, respectively. EDDC declined across successive cohorts, whereas the prevalence of overweight/obesity at age 50 increased. EDDC and overweight/obesity were associated with higher odds of reporting diabetes. A scenario that eliminates disadvantaged EDDC reduced diabetes prevalence by 11% in a pooled sample, while eliminating overweight/obesity reduced it by 30%. Overweight/obesity explained 42% of the rise in diabetes prevalence between the 1930-1939 and 1950-1959 cohorts. Improvement in EDDC explained 18% of the rise in diabetes prevalence between 1930-1939 and 1950-1959 cohorts. High body weight across Mexican birth cohorts seemed to offset the potential benefits from improvements in childhood conditions on adult diabetes risk.

7328 A case of Adrenal Calcifications in a Patient with Familial Cerebral Cavernous Malformations

Abstract Disclosure: R.I. Dorin: None. L.E. Aguirre: None. M. Bomgardner: None. Background: Familial syndromes of cerebral cavernous malformation (fCCM) having autosomal dominant inheritance and variable penetrance and expression have been linked to loss of function mutations at three genetic loci. The association of small focal adrenal calcifications with fCCM was only recently recognized in a New Mexican cohort of subjects predominately carrying the founder common Hispanic mutation in the CCM1 locus (stop codon Q455X in the Krev1 interaction trapped gene 1 [KRIT1]). We report a case of bilateral, focal adrenal calcifications in a patient affected by fCCM. Clinical Case: A 72-year-old Hispanic male with past medical history of intracranial CCM was referred for osteoporosis and hyperthyroidism due to multinodular goiter. Small focal calcifications of the adrenal glands were incidentally noted on prior imaging studies. There was no history of anticoagulant use, adrenal hemorrhage, or systemic/adrenal infection. The patient was without clinical manifestations of adrenal insufficiency, morning cortisol and plasma ACTH concentrations were normal, and exam was negative for hyperpigmentation or cutaneous vascular malformations. Brain MRI revealed the presence of over 100 parenchymal CCM lesions. A family history of CCM was reported in multiple family members, including 7/10 siblings. Conclusion: In addition to cutaneous malformations, small focal adrenal calcifications are now recognized as one of the extra-neurological manifestations of fCCM, particularly in patients harboring the common Hispanic CCM1/KRIT1 mutation. Whether adrenal calcifications are observed in fCCM patients having other mutations of KRIT1 or other genetic loci of fCCM (CCM2 or PDCD10) remains to be determined. The focal adrenal calcifications are believed to be result of dyssynchronous, subclinical hemorrhagic events related to vascular malformations in the adrenal gland. These findings implicate a role for KRIT1 in endothelial development in the adrenal gland in addition to established role in CNS, spinal cord, and skin. Our patient appeared had normal adrenocortical function, as expected for the focal nature of the adrenal lesions. Though adrenal function has not been evaluated in fCCM patients, there are no reports of primary adrenal insufficiency in fCCM in the literature. Adrenal calcifications may be considered to represent an imaging biomarker for fCCM, and fCCM should be included in the differential diagnosis of adrenal calcifications. The incidental recognition of characteristic small, focal adrenal calcifications in either bilateral or unilateral adrenal glands should prompt evaluation for fCCM.

Postoperative Pain at Discharge From the Post-anesthesia Care Unit: A Case-Control Study.

Despite advancements in postoperative pain management, approximately 20% of patients still experience severe pain within the first 24 hours post-surgery. Previous studies utilizing machine learning have shown promise in predicting postoperative pain with various models. This study investigates postoperative pain predictors using a machine learning approach based on physiological indicators and demographic factors in a Mexican cohort. We conducted a retrospective case-control study to assess pain determinants at Post-anesthesia Care Unit (PACU) discharge at Hospital Ángeles Lomas in Mexico City. Data were collected from 550 patients discharged from the PACU, including 292 cases and 258 controls, covering a range of surgical procedures and illnesses. Machine learning techniques were employed to develop a predictive model for postoperative pain. Physiological responses, such as blood pressure, heart rate, respiratory rate, and anesthesia type, were recorded prior to PACU admission. Significant differences were found between cases and controls, with factors such as sex, anesthesia type, and physiological responses influencing postoperative pain. Visual analog scale (VAS) scores at PACU admission were predictive of pain at discharge. Our findings reinforce existing literature by highlighting sex-based disparities in pain experiences and the influence of anesthesia type on pain levels. The logistic regression model developed, incorporating physiological responses and sex, shows potential for refining pain management strategies. Limitations include the lack of detailed surgical data and psychological factors, and validation in a prospective cohort. Future research should focus on more comprehensive predictive models and longitudinal studies to further improve postoperative pain management.

Performance of the 2023 American College of Rheumatology/EULAR Classification Criteria for Antiphospholipid Syndrome in a Mexican Cohort.

The objective is to assess the performance of the 2023 American College of Rheumatology/EULAR classification criteria (2023 AECC) for antiphospholipid syndrome (APS) in a Mexican cohort. We enrolled patients with primary APS (PAPS) and secondary APS (SAPS) and a control group of nonautoimmune thrombophilia. We evaluated the fulfillment of the 2023 AECC and the 2006 revised Sapporo classification criteria (2006 RSCC) and their performance against the clinical diagnosis as the gold standard. The baseline Global APS Score (GAPSS) and the Damage Index for APS (DIAPS) at last follow-up were calculated. We included 85 patients with PAPS, 54 with SAPS, and 50 with thrombophilia. According to the 2023 AECC criteria, 69 patients (81.2%) with PAPS, 28 patients (51.9%) with SAPS, and none of the patients with thrombophilia met the criteria. When comparing true positive (TP) (n = 69) versus false negative (n = 16) cases within the PAPS group, TP cases exhibited a higher frequency of thrombotic manifestations and IgM anti-cardiolipin and IgG anti-β2-glycoprotein-I positivity. For PAPS, there was a correlation between the 2023 AECC score and both GAPSS (rho = 0.621, P < 0.0001) and DIAPS scores (rho = 0.433, P < 0.0001). When comparing the 2023 AECC with the 2006 RSCC, a lower sensitivity (81.2% vs 88.2%) but a higher specificity (100.0% vs 92.0%) was observed for PAPS. Similar findings were observed in SAPS. In both PAPS and SAPS, the 2023 AECC have higher specificity than the 2006 RSCC. The main feature of patients with PAPS according to the 2023 AECC was thrombosis. These criteria might identify patients at higher risk of thrombosis and damage accrual.

Selection scan in Native Americans of Mexico identifies FADS2 rs174616: Evidence of gene-diet interactions affecting lipid levels and Delta-6-desaturase activity

Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.

Factors that Influence Growth Rates of Abdominal Aortic Aneurysms. Analysis of a Mexican Cohort.

Abdominal Aortic Aneurysms (AAA) growth remains a process not fully understood. The objective of this study was to analyze risk factors associated with changes in AAA diameter in a Mexican cohort. An observational study in which we analyzed the entirely of patients in which an AAA was reported in a Computed Tomography (CT) study from 2014 to 2021 who had a follow-up CT. We divided them by groups depending on the diagnosis of type 2 diabetic mellitus and pharmacological history (diabetic vs non-diabetic, metformin vs non-metformin intake and statin vs non-statin intake). We compared pre and post follow-up AAA diameters using paired t-tests. A multivariate analysis was performed in order to identify independent variables associated with an increased growth rate. Statistical analysis was performed on Stata 17. During the studied period 72 (39.77%) patients had a follow-up CT. Mean age was 75years (±9.05) and 52 (72.22%) were men. When comparing infra-renal largest diameter through time based on metformin intake, a significant difference was found only in the metformin non-intake group (42.05 ± 12.54 vs45.34 ± 12.06 [P = 0.02]), in contrast the metformin intake group measures were non-significantly different (36.13 ± 7.04 vs 37.00 ± 4.51; P = 0.57) through follow-up. In the multivariate analysis AAA largest diameter at diagnosis correlated with significantly increased growth rate (coeff = 0.06, P < 0.05). AAA diameters appear to change through time in a non-linear pattern influenced by different epidemiological and clinical factors. Metformin intake appears to promote a stability in AAA diameter growth in our studied population.

Cytogenomic description of a Mexican cohort with differences in sex development

BackgroundDifferences in Sex Development (DSD) is a heterogeneous group of congenital alterations that affect inner and/or outer primary sex characters. Although these conditions do not represent a mortality risk, they can have a severe psycho-emotional impact if not appropriately managed. The genetic changes that can give rise to DSD are diverse, from chromosomal alterations to single base variants involved in the sexual development network. Epidemiological studies about DSD indicate a global frequency of 1:4500–5500, which can increase to 1:200–300, including isolated anatomical defects. To our knowledge, this study is the first to describe epidemiological and genetic features of DSD in a cohort of Mexican patients of a third-level care hospital.MethodsDescriptive and retrospective cross-sectional study that analyzed DSD patients from 2015 to 2021 attended a Paediatric Hospital from Mexico City.ResultsOne hundred one patients diagnosed with DSD were registered and grouped into different entities according to the Chicago consensus statement and the diagnosis defined by the multidisciplinary group. Of the total, 54% of them belong to the chromosomal DSD classification, 16% belongs to 46, XX and 30% of them belongs to the 46, XY classification.ConclusionThe frequency for chromosomal DSDs was consistent with the literature; however, we found that DSD 46, XY is more frequent in our cohort, which may be due to the age of the patients captured, the characteristics of our study population, or other causes that depend on the sample size.

Diagnostic performance of sixteen biomarkers for MASLD: A study in a Mexican cohort

Background and aimsMetabolic Dysfunction-associated Steatotic Liver Disease (MASLD) poses a heightened cardiovascular risk. Identifying efficient biomarkers for early MASLD detection in resource-limited Latin American regions is crucial. We aimed to evaluate the diagnostic efficacy of sixteen biomarkers for MASLD in Mexican individuals. MethodsIn this cross-sectional and analytical study, steatosis was assessed using vibration-controlled transient elastography. MASLD was defined according to international standards. Assessed biomarkers included: Visceral Fat (VF), Waist Circumference (WC), Waist-Height Ratio (WHtr), Waist-Hip Ratio (WHr), Visceral Adiposity Index (VAI), Hepatic Steatosis Index (HSI), Body Mass Index (BMI), Homeostatic Model Assessment (HOMA), Weight-Adjusted-Waist Index (WWI), Lipid Accumulation Product (LAP), Uric Acid-Creatinine Ratio (UACR), Triglyceride-Glucose Index (TyG) and its variants TyG-WC, TyG-HDL, TyG-BMI, TyG-WHtr. Results161 participants were included, of which 122 met MASLD criteria (56 % women, age 53.9 years [47.5–64]) and 39 were healthy controls (76 % women, age 52 [45–64]). The AUROCs of the biomarkers for MASLD were: TyG-WC (0.84), LAP (0.84), TyG-BMI (0.82), TyG-WHtr (0.80), WC (0.78), TyG (0.77), WHtr (0.75), BMI (0.76), VF (0.75), HSI (0.75), TyG-HDL (0.75), WHr (0.72), VAI (0.73), UA/CR (0.70), HOMA (0.71), and WWI (0.69). Sex-based differences were observed. After adjusting for sociodemographic variables, the TyG-WC index was the best predictor of MASLD. ConclusionsIn conclusion, our results underscore the potential of several noninvasive biomarkers for MASLD assessment in a Mexican population, highlighting variations in diagnostic efficacy and cut-off values between sexes. After adjusting, TyG-WC was the best MASLD predictor.

Diagnostic differences in high-resolution esophageal motility in a large Mexican cohort based on geographic distribution.

High-resolution esophageal manometry [HRM] has become the gold standard for the evaluation of esophageal motility disorders. It is unclear whether there are HRM differences in diagnostic outcome based on regional or geographic distribution. The diagnostic outcome of HRM in a diverse geographical population of Mexico was compared and determined if there is variability in diagnostic results among referral centers. Consecutive patients referred for HRM during 2016-2020 were included. Four major referral centers in Mexico participated in the study: northeastern, southeastern, and central (Mexico City, two centers). All studies were interpreted by experienced investigators using Chicago Classification 3 and the same technology. A total of 2293 consecutive patients were included. More abnormal studies were found in the center (61.3%) versus south (45.8%) or north (45.2%) P< 0.001. Higher prevalence of achalasia was noted in the south (21.5%) versus center (12.4%) versus north (9.5%) P< 0.001. Hypercontractile disorders were more common in the north (11.0%) versus the south (5.2%) or the center (3.6%) P.001. A higher frequency of weak peristalsis occurred in the center (76.8%) versus the north (74.2%) or the south (69.2%) P< 0.033. Gastroesophageal junction obstruction was diagnosed in (7.2%) in the center versus the (5.3%) in the north and (4.2%) in the south p.141 (ns). This is the first study to address the diagnostic outcome of HRM in diverse geographical regions of Mexico. We identified several significant diagnostic differences across geographical centers. Our study provides the basis for further analysis of the causes contributing to these differences.

TEK gene-related primary congenital glaucoma: Phenotypic features and mutational spectrum in a Mexican cohort of 10 unrelated families.

Primary congenital glaucoma (PCG) is one of the leading causes of visual damage and blindness, severely affecting the quality of life of affected children. It is characterized by cupping of the optic disc and loss of ganglion cells due to elevated intraocular pressure. While most PCG patients exhibit epiphora, photophobia, and buphthalmos with corneal opacity, variability in phenotypic manifestations is not uncommon. Prompt diagnosis and treatment of PCG affected individuals becomes relevant to preserve visual function throughout their lives. Most PCG cases are sporadic or autosomal recessive; however, an incompletely dominant autosomal dominant form arising from mutations in the TEK gene has recently been demonstrated. Here, we describe the clinical and mutational features of a cohort of Mexican patients with TEK-related PCG. Our results support the involvement of the TEK gene as an important cause of the disease in our ethnic group and expand the mutational spectrum causing PCG by reporting 10 novel disease-causing variants.

Predictive models as a clinical decision support tool for genetic cancer risk assessment among Mexican patients at risk of hereditary colorectal cancer.

10617 Background: Hereditary cancer syndromes, including Lynch syndrome (LS) with an increased risk of colorectal cancer (CRC), have prompted the development of clinical criteria and predictive models (PM) to identify at-risk individuals. However, these criteria have been validated with limited representation from the Latino population. Several factors may influence CRC penetrance, potentially leading to variations in PM performance across populations. Given that CRC ranks as the third most prevalent cancer worldwide, the increasing incidence of early-onset disease highlights the need for expanding Genetic Cancer Risk Assessment (GCRA) services. Methods: This prospective study included Mexican patients who were diagnosed with CRC and met NCCN criteria for GCRA. Participants were enrolled at two referral centers in Mexico, the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City and at the Hospital Zambrano Hellion TecSalud, Nuevo Leon. Participants' carrier risk was estimated using the PREMM5 model. Amsterdam II and revised Bethesda criteria, immunohistochemistry (IHC) for DNA mismatch repair (MMR) proteins in tumor tissue and multigene panel testing results were reviewed. For this analysis, only pathogenic and likely pathogenic (P/LP) variants in probands were reported. Results: From April 2016 to October 2023, 194 patients were included, with a median age at diagnosis of 45.0 (range 17-82) years, and 49.5% were women. P/LP variants were identified in 37.6% (n=73). 27.5% (n=50) were carriers of P/LP variants associated with LS (29 MLH1, 13 MSH2, 6 MSH6, and 2 PMS2). 11.8% (n=23) were carriers of P/LP variants in other genes (7 APC, 4 ATM, 3 CHEK2, 2 BRCA1, 2 TP53, 2 STK11, 1 PALB2, 1 BRIP1, and 1 MUTYH). Overall, carriers of PVs were diagnosed with CRC at a younger age than non-carriers (42 vs 46 years, p=0.034). The Amsterdam II criteria proved to be accurate (Sen 55%, Spe 91%, PPV 0.69, NPV 0.85), while the Bethesda criteria (Sen 98%, Spe 18%, PPV 0.29, NPV 0.96) and IHC for MMR proteins (Sen 94%, Spe 67%, PPV 0.61, NPV 0.95) were found to be highly sensitive. The area under the ROC curve for PREMM5 was 0.82 with a mean score 28.5 (2.1 – 50) in patients with LS and 6.0 (0.9 – 50) in non-carriers. Carriers of PVs had a higher rate of multiple primary malignancies than non-carriers (41.0% vs 19.0%, p=0.0014), and self-reported family history of CRC (65.7% vs 24.8%, p&lt;0.001). Conclusions: Our results showed the PREMM5 model and IHC for MMR proteins effectively prioritized patients eligible for germline genetic testing in resource-limited settings. The performance of PREMM5 in this Mexican cohort was similar to that reported in the validation study of this model in other populations. Considering the spectrum of identified P/LP variants, the multigene panel test should be used in the comprehensive evaluation of Mexican patients with CRC.

Presence of SARS-CoV-2-specific T cells before vaccination in the Mexican population.

The immune response to SARS-CoV-2 has been extensively studied following the pandemic outbreak in 2020; however, the presence of specific T cells against SARS-CoV-2 before vaccination has not been evaluated in Mexico. In this study, we estimated the frequency of T CD4+ and T CD8+ cells that exhibit a specific response to S (spike) and N (nucleocapsid) proteins in a Mexican population. We collected 78 peripheral blood samples from unvaccinated subjects and the presence of antibodies against spike (RBD) and N protein was determined. PBMCs (peripheral blood mononuclear cells) were isolated and stimulated with a pool of S or N protein peptides (Wuhan-Hu-1 strain). IL-1β, IL-4, IL-6, IL-10, IL-2, IL-8, TNF-α, IFN-γ, and GM-CSF levels were quantified in the supernatant of the activated cells, and the cells were stained to assess the activation and memory phenotypes. Differential activation frequency dependent upon serological status was observed in CD4+ cells, but not in CD8+ cells. The predominantly activated population was the central memory T CD4+ cells. Only 10% of the population exhibited the same phenotype with respect to the response to nucleocapsid peptides. The cytokine profile differed between the S and N responses. S peptides induced a more proinflammatory response compared with the N peptides. In conclusion, in a Mexican cohort before vaccination, there was a significant response to the S and N SARS-CoV-2 proteins resulting from previous infections with seasonal coronaviruses or previous undetected exposure to SARS-CoV-2.

Exploring the relationship between admixture and genetic susceptibility to attention deficit hyperactivity disorder in two Latin American cohorts

Contemporary research on the genomics of Attention Deficit Hyperactivity Disorder (ADHD) often underrepresents admixed populations of diverse genomic ancestries, such as Latin Americans. This study explores the relationship between admixture and genetic associations for ADHD in Colombian and Mexican cohorts. Some 546 participants in two groups, ADHD and Control, were genotyped with Infinium PsychArray®. Global ancestry levels were estimated using overall admixture proportions and principal component analysis, while local ancestry was determined using a method to estimate ancestral components along the genome. Genome-wide association analysis (GWAS) was conducted to identify significant associations. Differences between Colombia and Mexico were evaluated using appropriate statistical tests. 354 Single-nucleotide polymorphisms (SNPs) and Single-nucleotide variants (SNVs) related to some genes and intergenic regions exhibited suggestive significance (p-value < 5*10e−5) in the GWAS. None of the variants revealed genome-wide significance (p-value < 5*10e−8). The study identified a significant relationship between risk SNPs and the European component of admixture, notably observed in the LOC105379109 gene. Despite differences in risk association loci, such as FOXP2, our findings suggest a possible homogeneity in genetic variation’s impact on ADHD between Colombian and Mexican populations. Current reference datasets for ADHD predominantly consist of samples with high European ancestry, underscoring the need for further research to enhance the representation of reference populations and improve the identification of ADHD risk traits in Latin Americans.

Differences between radiographic and non-radiographic axial spondyloarthritis patients in a Mexican cohort

To compare the demographic, clinical, and laboratory characteristics, disease onset, and clinical features of radiographic axial Spondyloarthritis (r-axSpA) and non-radiographic axial Spondyloarthritis (nr-axSpA) patients. All patients who attended outpatient spondylarthritis (SpA) clinics at Hospital General de Mexico and the Instituto Nacional de la Nutrición from 1998 to 2005 and met the rheumatologist diagnostic criteria for SpA were selected. Then the SpA patients were classified by European Spondyloarthropathy Study Group criteria (ESSG). We selected SpA patients with axial presentation as axial SpA (axSpA), and they were classified as r-axSpA if they met modified New York (mNY) criteria for sacroiliitis and as nr-axSpA if they did not meet mNY criteria; to compared clinical, demographic, and laboratory test between the subgroups. It included 148 SpA patients; 55 (37.2%) patients had r-axSpA, and 70 (47.3%) had nr-axSpA. The nr-axSpA patients had a lower proportion of males (58.6% vs 78.2%, P < 0.05), lower HLA-B27 frequency (54.3%. vs. 92.7%, P < 0.05), were older at disease onset (21 vs 16 years; P < 0.01) and had a higher frequency of infections at disease onset (9.1% vs 32.9, P < 0.05) than r-axSpA. BASFI (2.9 vs 4.8; P < 0.0001), Dougados functional index (7 vs. 14; P < 0.05), and BASDAI (4.1 vs. 5.2; P < 0.001) were lower in patients with nr-axSpA than r-axSpA, respectively. The factors that most influenced the presentation of r-axSpA were history of uveitis (OR 14, 95% CI 2.3–85), HLA-B27 (OR 7.97, 95% CI, 2.96–122), male sex (OR 6.16, 95% CI, 1.47–25.7), axial enthesopathy count (OR 1.17 95% CI, 1.03–1.33). This study provides insight into the differences between nr-axSpA and r-axSpA in Mexico. Patients with r-axSpA were mainly male, with a younger presentation age, a higher prevalence of HLA-B27, more history of uveitis, fewer episodes of dactylitis, more axial enthesopathy, and higher disease activity than nr-axSpA.