Mexican Biobank advances population and medical genomics of diverse ancestries.

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database.

The role of SLC16A11 variations in diabetes mellitus.

Purpose Of Review: The aim of this study was to summarize the existing evidence that proves the association between an ethnic-specific SLC16A11 risk haplotype and type 2 diabetes found in the Latin American population.

Recent Findings: The association has been replicated in consortia studies, especially in early-onset type 2 diabetes. No association has been found with gestational diabetes.

A novel nonsense mutation in the insulin receptor gene in a patient with HAIR-AN syndrome and endometrial cancer.

Severe insulin resistance can be caused by rare genetic defects in the insulin receptor known as insulin receptoropathies. These genetic defects cause a wide spectrum of clinical manifestations ranging from mild syndromes to lethal disorders. Among those is the HAIR-AN an extreme subtype of polycystic ovary syndrome (PCOS).

Critical role of acute hypoxemia on the cognitive impairment after severe COVID-19 pneumonia: a multivariate causality model analysis.

Background: A high proportion of coronavirus disease 2019 (COVID-19) survivors may develop long-term cognitive impairment. We aimed to develop a multivariate causal model exposing the links between COVID-19-associated biomarkers, illness-related variables, and their effects on cognitive performance.

Methods: In this prospective study, we assess the potential drivers for the development of cognitive impairment in patients with severe COVID-19 pneumonia aged ≥ 18 years at 6-month follow-up after hospital discharge, using the Montreal Cognitive Assessment (MoCA).

Identification of TBX15 as an adipose master trans regulator of abdominal obesity genes.

Background: Obesity predisposes individuals to multiple cardiometabolic disorders, including type 2 diabetes (T2D). As body mass index (BMI) cannot reliably differentiate fat from lean mass, the metabolically detrimental abdominal obesity has been estimated using waist-hip ratio (WHR). Waist-hip ratio adjusted for body mass index (WHRadjBMI) in turn is a well-established sex-specific marker for abdominal fat and adiposity, and a predictor of adverse metabolic outcomes, such as T2D.

Differentiating Among Type 1, Type 2 Diabetes, and MODY: Raising Awareness About the Clinical Implementation of Genetic Testing in Latin America.

Objective: To describe a case of maturity-onset diabetes of the young (MODY) to highlight the importance of a correct diabetes diagnosis.

Methods: We describe a Mexican family misdiagnosed with T1D and T2D.

Results: A 36-year-old woman with diabetes and adverse outcomes during 2 pregnancies had been diagnosed with T2D 10 years ago.

Familial hypertriglyceridemia: an entity with distinguishable features from other causes of hypertriglyceridemia.

Background: Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease.

Methods: This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls.

Use of PCSK9 Inhibitor in a Mexican Boy with Compound Heterozygous Familial Hypercholesterolemia: A Case Report.

We report on the case of an 8-year-old Mexican male, with a 3-year-old clinical diagnosis of familial hypercholesterolemia, and the difficulties encountered in his treatment while in our care. His treatment started with a regimen consisting of ezetimibe/simvastatin, cholestyramine, and a dietary plan of 1600 calories, with a limited intake of 200 mg of cholesterol per day. Problems arose when the patient's low-density lipoprotein cholesterol (LDL) levels did not meet ideal targets, which prompted the use of LDL cholesterol apheresis (not available in Mexico) for 6 months.

Development and validation of a predictive model for incident type 2 diabetes in middle-aged Mexican adults: the metabolic syndrome cohort.

Background: Type 2 diabetes mellitus (T2D) is a leading cause of morbidity and mortality in Mexico. Here, we aimed to report incidence rates (IR) of type 2 diabetes in middle-aged apparently-healthy Mexican adults, identify risk factors associated to ID and develop a predictive model for ID in a high-risk population.

Methods: Prospective 3-year observational cohort, comprised of apparently-healthy adults from urban settings of central Mexico in whom demographic, anthropometric and biochemical data was collected.

The SLC16A11 risk haplotype is associated with decreased insulin action, higher transaminases and large-size adipocytes.

Objective A haplotype at chromosome 17p13 that reduces expression and function of the solute carrier transporter SLC16A11 is associated with increased risk for type 2 diabetes in Mexicans. We aim to investigate the detailed metabolic profile of SLC16A11 risk haplotype carriers to identify potential physiological mechanisms explaining the increased type 2 diabetes risk. Design Cross-sectional study.

Mexican Carriers of the p.E508K Variant Do Not Experience an Enhanced Response to Sulfonylureas.

Objective: To assess whether an ethnic-specific variant (p.E508K) in the maturity-onset diabetes of the young (MODY) gene hepatocyte nuclear factor-1α () found in Mexicans is associated with higher sensitivity to sulfonylureas, as documented in patients with MODY3.

Research Design And Methods: We recruited 96 participants (46 variant carriers and 50 age- and sex-matched noncarriers).

The panorama of familial hypercholesterolemia in Latin America: a systematic review.

The burden caused by familial hypercholesterolemia (FH) varies among countries and ethnic groups. The prevalence and characteristics of FH in Latin American (LA) countries is largely unknown. We present a systematic review (following the PRISMA statement) of FH in LA countries.

Factors associated with postprandial lipemia and apolipoprotein A-V levels in individuals with familial combined hyperlipidemia.

Background: Alterations in postprandial metabolism have been described in familial combined hyperlipidemia (FCH); however, their underlying mechanisms are not well characterized. We aimed to identify factors related to the magnitude of postprandial lipemia and apolipoprotein (apo) A-V levels in subjects with FCH.

Methods: FCH cases (n = 99) were studied using a standardized meal test.

[Thyroid hormone resistance (THR): a case report].

Thyroid hormone resistance is a syndrome characterized by a reduced response to thyroid hormone with different degrees of resistance at target tissues. We present the clinical features, physical findings, and study protocol in a woman with thyroid hormone resistance. An arginine to tryptophan mutation on the β isoform of the thyroid hormone receptor gene was demonstrated.

The R230C variant of the ATP binding cassette protein A1 (ABCA1) gene is associated with a decreased response to glyburide therapy in patients with type 2 diabetes mellitus.

Objective: To test the hypothesis that persons with the R230C allele of ABCA1 show a decreased glycemic response to glyburide. This polymorphism is exclusively found in Ameri-indian populations and is associated with type 2 diabetes.

Research Design And Methods: This is a single blind controlled study including participants with type 2 diabetes (fasting glucose levels 126-250 mg/dl and HbA1c 7%-10%) managed with metformin and a lifestyle program.

Contribution of common genetic variation to the risk of type 2 diabetes in the Mexican Mestizo population.

Several studies have identified nearly 40 different type 2 diabetes susceptibility loci, mainly in European populations, but few of them have been evaluated in the Mexican population. The aim of this study was to examine the extent to which 24 common genetic variants previously associated with type 2 diabetes are associated in Mexican Mestizos. Twenty-four single nucleotide polymorphisms (SNPs) in or near genes (KCNJ11, PPARG, TCF7L2, SLC30A8, HHEX, CDKN2A/2B, CDKAL1, IGF2BP2, ARHGEF11, JAZF1, CDC123/CAMK1D, FTO, TSPAN8/LGR5, KCNQ1, THADA, ADAMTS9, NOTCH2, NXPH1, RORA, UBQLNL, and RALGPS2) were genotyped in Mexican Mestizos.

Primary amenorrhea in two sisters: description of a Mexican family with 17α hydroxylase-17 lyase deficiency caused by arginine - stop mutation.

A rare cause of congental adrenal hyperplasia is 17α-hydroxylase deficiency. It results in sexual infantilism, primary amenorrhea in females, pseudohermaphroditism in males, hypertension, and hypokalemia. We studied two female siblings from a rural community in Mexico.

[Familial homozygous hypercholesterolemia due to the c2271delT mutation in the LDL receptor gene, detected exclusively in Mexicans].

We present the case of an 18-years old women with homozygous familial hypercholesterolemia in which a LDL receptor mutation (c2271delT) was found. This mutation has been informed only in Mexicans. The patient was born in Oaxaca, Mexico.

Familial hypobetalipoproteinemia in a hospital survey: genetics, metabolism and non-alcoholic fatty liver disease.

Introduction: Familial hypobetalipoproteinemia (FHBL) is an autosomal dominant disease characterized by abnormally low levels of apolipoprotein-B (apoB) containing lipoproteins. FHBL is caused by APOB, PCSK9 or ANGPTL3 mutations or is associated with loci located in chromosomes 10 and 3p21. However, other genes should be involved.

The non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 is associated with low HDL cholesterol concentrations in Mexican adults: a population based nation wide study.

Objective: To search for an association between the non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 and low HDL cholesterol levels in a Mexican, population-based nation wide survey.

Methods: The 2000 National Health Survey is a cross sectional study that included individuals from 400 cities. All individuals who had a 9-12-h fasted blood sample and a DNA sample were selected (n = 1729).

[Fifty years studying hiperlipidemias: the case of familial combined hyperlipidemia].

Familial combined hyperlipidemia (FCHL) is the most frequent primary dyslipidemia. Its manifestations include hypercholesterolemia, hypertriglyceridemia or the combination of both abnormalities. In spite of its high frequency, the proper diagnosis is rarely done.