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INTRODUCTION: The ATXN2 gene has a VNTR (CAG)n with locus in exon1. Long alleles within the normal range (22-29 repeats) are associated with severe obesity in people from the United Kingdom, Indonesia and the Caribbean. OBJECTIVE: To analyse the influence of VNTR (CAG)n on metabolic profile in adults with obesity and pre-obesity, as well as to estimate its effect on the risk of developing diabetes. METHODS AND MATERIAL: 255 adults of Chinantec Amerindian ethnic origin were included, who underwent anthropometric and biochemical evaluation. The VNTR was amplified by end-point PCR and by 8% PAGE electrophoresis. RESULTS: Differences were found in the waist/hip circumference index and body mass index in the carriers of genotypes different to the one homozygous for 22 repeats with a Student's t-test value of 0.0041 and 0.0334, respectively. We also found an association with a family history of chronic disease. CONCLUSION: The VNTR of ATXN2 is associated with obesity in Mexican adults of Chinantec ancestry.
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Enfermedades Cardiovasculares , Adulto , Ataxina-2/genética , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Obesidad/genética , Polimorfismo Genético , Factores de RiesgoRESUMEN
Hypertension is a major public health problem, affecting more than a quarter of the world's population causing serious cardiovascular problems. In recent years, different polymorphisms have been studied and helped to identify some candidate genes and hereditary syndromes associated with the molecular mechanisms involved in the development of hypertension. Therefore, it is important to identify these molecular mechanisms. This review exposes all the genes and polymorphisms that increase or decrease the risk of hypertension in different populations that are related to the renin angiotensin aldosterone system, G protein, salt excretion, aldosterone synthesis, lipid metabolism, mechanism of insulin resistance, vitamin metabolism, purines and sodium reabsorption. This document can be a useful tool in clinical practice, in addition to serving as a support for future research on this topic.
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Hipertensión , Aldosterona , Dieta , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/genética , Polimorfismo Genético , Renina , Sistema Renina-Angiotensina/genética , Cloruro de Sodio DietéticoRESUMEN
OBJECTIVE: To estimate the correlation between indices of diet quality (DQIs), insulin sensitivity (QUICKI) and resistance (HOMA-IR), waist circumference (WHR) and body mass (BMI) and the alleles and genotypes of the TJP1 SNP rs2291166 and the VNTR of ATXN2 in adolescent patients. SUBJECTS AND METHOD: The study enrolled 85 subjects aged 10-20years, from the city of Tuxtepec, Oaxaca, Mexico, recruited in the period 2017-2018. DQIs, BMI, WHR, HOMA-IR, QUICKI, and diet quality index were measured. The rs2291166 polymorphism in TJP1 was determined by allele-specific PCR and the (CAG)n expansion in ATXN2 was determined by hot start PCR. PCR products were analyzed using 8% PAGE electrophoresis and silver nitrate staining. RESULTS: A correlation was found of indices DQIs, HOMA-IR, WHR and BMI with the heterozygous genotype of the TJP1 SNP rs2291166 and the long and short repeats of the ATXN2 CAG repeat in obese adolescent patients. A very strong positive correlation was seen between the TJP1 SNP and the HOMA-IR index (P<.05). A positive correlation was also found between the ATXN2 CAG repeat and the QUICKI index (P=.000) (P<.05), while the DQIs index correlated more closely with BMI and WHR. CONCLUSIONS: DQIs, TJP1 SNP rs2291166, and ATXN2 CAG repeat are determinants of obesity-related risk parameters such as BMI, WHR, QUICKI, and HOMA-IR in the adolescent population analyzed.
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Oxidation of glucose is the major source of obtaining cell energy, this process requires glucose transport into the cell. However, cell membranes are not permeable to polar molecules such as glucose; therefore its internalization is accomplished by transporter proteins coupled to the cell membrane. In eukaryotic cells, there are two types of carriers coupled to the membrane: 1) cotransporter Na+-glucose (SGLT) where Na+ ion provides motive power for the glucose´s internalization, and 2) the glucotransporters (GLUT) act by facilitated diffusion. This review will focus on the 14 GLUT so far described. Despite the structural homology of GLUT, different genetic alterations of each GLUT cause specific clinical entities. Therefore, the aim of this review is to gather the molecular and biochemical available information of each GLUT as well as the particular syndromes and pathologies related with GLUT´s alterations and their clinical approaches.
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Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Glucosa/metabolismo , Transporte Biológico , Membrana Celular/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/genética , HumanosRESUMEN
BACKGROUND: TJP1 gene encodes a ZO-1 protein that is required for the recruitment of occludins and claudins in tight junction, and is involved in cell polarisation. It has different variations, the frequency of which has been studied in different populations. In Mexico there are no studies of this gene. These are required because their polymorphisms can be used in studies associated with medicine and surgery. Therefore, the aim of this study was to estimate the frequency of alleles and genotypes of rs2291166 gene polymorphism TJP1 in Mexico Mestizos population, and to estimate the conformational effect of an amino acid change. MATERIAL AND METHODS: A total of 473 individuals were included. The rs2291166 polymorphism was identified PASA PCR-7% PAGE, and stained with silver nitrate. The conformational effect of amino acid change was performed in silico, and was carried out with servers ProtPraram Tool and Search Database with Fasta. RESULTS: The most frequent allele in the two populations is the ancestral allele (T). A genotype distribution similar to other populations was found. The polymorphism is in Hardy-Weinberg, p>0.05. Changing aspartate to alanine produced a conformational change. CONCLUSIONS: The study reveals a high frequency of the ancestral allele at rs2291166 polymorphism in the Mexican population.
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Etnicidad/genética , Polimorfismo de Nucleótido Simple , Proteína de la Zonula Occludens-1/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Simulación por Computador , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Mola Hidatiforme/genética , Indígenas Norteamericanos/genética , Masculino , Matrimonio , México , Persona de Mediana Edad , Modelos Genéticos , Modelos Moleculares , Datos de Secuencia Molecular , Síndromes Neoplásicos Hereditarios/genética , Pancreatitis/genética , Embarazo , Conformación Proteica , Estabilidad Proteica , España/etnología , Adulto Joven , Proteína de la Zonula Occludens-1/químicaRESUMEN
El locus g.37190613 en 7p14.2-14.1 del gen ELMO1 presenta un polimorfismo el cual consiste en un cambio G>A(rs1345365). Esta variante, entre otras, de ELMO1, ha sido asociada con nefropatía diabética en diferentes poblaciones. En México son limitados los estudios de asociación de diabetes mellitus con genes candidatos. Por ello, el objetivo del presente trabajo fue determinar la asociación del SNP rs1345365 del gen ELMO1 con el desarrollo de diabetes mellitus tipo 2 (DM2). Para ello se analizaron 148 pacientes con DM2, 156 individuos sin diabetes pero con factores de riesgo cardiovascular y 269 personas sanas sin DM2. El polimorfismo se identificó por PASA (PCR AMPLIFICATION ALLELE SPECIFIC) y PAGE teñida con nitrato de plata. La asociación se estableció por diferentes modelos de epidemiología genética; el modelo dominante mostró una asociación positiva (p=0,0006) como factor protector y el para-dominante mostró al estado heterocigoto como factor de riesgo. En conclusión el estudio reveló la asociación del SNP rs1345365 del gen ELMO1 con DM2 en una población mestiza Mexicana.
The g.37190613 locus on 7p14.2-14.1 in the ELMO1 gene has a G>A polymorphism (SNP rs1345365) that has been associated with diabetic nephropathy in different populations. The genetic-association studies in type 2 diabetes mellitus (DM2) on the Mexican population are limited. The aim of this study was to estimate whether the polymorphism G>A of ELMO1 gene is associated with the development of DM2. We included 148 DM2 individuals, 156 individuals with cardiovascular risk factors without diabetes and 269 healthy proband without DM2. The polymorphism was identified by PCR amplification specific allele (PASA), PAGE and silver staining. The association was established by genetic epidemiological models; the dominant model showed a positive association (p=0.0006) as a protective factor, and the para-dominant model to heterozygous, as risk factor. In conclusion, this study revealed the association of the SNP rs1345365 of the ELMO1 gene in a Mexican population.
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Adulto , Humanos , Masculino , Persona de Mediana Edad , Proteínas Adaptadoras Transductoras de Señales/genética , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Grupos Raciales , MéxicoRESUMEN
Multiple sclerosis is the most common cause of progressive neurological disability in young adults. This disease involves damage to the myelin sheath that normally insulates the electrical activity of nerve fibers. This leads to a wide range of symptoms as specific nerves become injured and lose their function. Epidemiological and experimental studies show that genetic alterations, antioxidant enzyme abnormalities and autoimmunity are risk factors for developing the disease. Recent evidence suggests that inflammation and oxidative stress within the central nervous system are major causes of ongoing tissue damage. Resident central nervous system cells and invading inflammatory cells release several reactive oxygen and nitrogen species which cause the histopathological features of multiple sclerosis: demyelization and axonal damage. The interplay between inflammatory and neurodegenerative processes results in an intermittent neurological disturbance followed by progressive accumulation of disability. Reductions in inflammation and oxidative stress status are important therapeutic strategies to slow or halt the disease processes. Therefore, several drugs are currently in trial in clinical practice to target this mechanism; particularly the use of supplements such as antioxidants and omega-3 polyunsaturated fatty acids, in order to improve the survival and quality of patients' lives.
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Diseño de Fármacos , Esclerosis Múltiple/fisiopatología , Neuronas/patología , Adulto , Antioxidantes/metabolismo , Axones/patología , Humanos , Inflamación/fisiopatología , Esclerosis Múltiple/tratamiento farmacológico , Estrés Oxidativo/fisiología , Calidad de Vida , Especies Reactivas de Oxígeno/metabolismo , Adulto JovenRESUMEN
Type 2 diabetes mellitus is a complex disease and a global health problem. Therefore, the first level of health care should handle the approaches of medical genetics and genomics to reduce its incidence. The aim is to present perspectives analyzed by our group in two areas of genetics and its clinical application. Emphasis is placed on the coexistence of several genetic forms clinically detectable in patients with diabetes, missing heritability associated with low penetrance, and epigenomics mechanism. It is discussed the effect of genetic variation associated with resistance to insulin, beta-cell dysfunction, shaft incretin, and other points of interest, such as thrifty genotype hypothesis, conformational disease, genetically unknown foods, phenocopies as clinically silent hypercortisolism, molecular phytopharmacology in the clinical management. Finally, the result was displayed in the Mexican population from genetic studies and new findings of clinical importance, such as involvement of melatonin and effect of variations in the number of copies in a genomic region.
La diabetes mellitus tipo 2 es una enfermedad multifactorial y un problema de salud mundial. De ahí que en el primer nivel de atención en salud se deben manejar los abordajes de la genética médica y genómica para disminuir su incidencia. El propósito de este artículo es presentar perspectivas analizadas por nuestro grupo en dos áreas de la genética, así como su aplicación clínica. Se hace hincapié en la coexistencia de varias formas genéticas clínicamente detectables en el paciente diabético, la heredabilidad perdida relacionada con baja penetrancia y fenómenos epigenómicos. Se discute el efecto de la variación genética relacionada con la resistencia a la insulina, la disfunción de las células beta, el eje incretínico, otros puntos de interés como las hipótesis del genotipo ahorrador, la patología conformacional, comidas genéticamente desconocidas, fenocopias como el hipercortisolismo clínicamente silente y la fitofarmacología molecular en el manejo clínico. Finalmente, se muestran resultados de estudios genéticos en población mexicana y nuevos hallazgos de importancia en la clínica, como la participación de la melatonina y el efecto de las variaciones en el número de copias en una región genómica.
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Diabetes Mellitus Tipo 2/genética , Genética Médica , Genómica , Atención Primaria de Salud , HumanosRESUMEN
Cockayne is a segmental progeroid syndrome that has autosomal recessive inheritance pattern. It is mainly characterized by Intrauterine growth retardation, severe postnatal growth deficiency, cachectic dwarfism, microcephaly, wizened face, sensorineural hearing loss, cataracts, dental caries, cardiac arrhythmias, hypertension, atherosclerosis, proteinuria, micropenis, renal failure, skeletal abnormalities, skin photosensitivity, decreased subcutaneous adipose tissue, cerebral atrophy, dementia, basal ganglia calcifications, ataxia and apraxia. It has a complex phenotype given by genetic heterogeneity. There are five gene responsible for this syndrome: CSA, CSB, XPB, XPD and XPG, in which various mutations have been found. The biochemical effect of these mutations includes dysfunctional protein of the repair system for oxidative damage to DNA, the complex coupled to transcription and the nucleotide excision repair system. Considering the role played for these proteins and its effects on clinical phenotype when they are deficient, we suggest that these genes might be candidates for analyzing susceptibility to common chronic degenerative diseases related to oxidative stress and aging.
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Síndrome de Cockayne/genética , Daño del ADN , Reparación del ADN/genética , Carbidopa/uso terapéutico , Síndrome de Cockayne/diagnóstico , Síndrome de Cockayne/tratamiento farmacológico , Síndrome de Cockayne/metabolismo , Síndrome de Cockayne/patología , ADN Helicasas/deficiencia , ADN Helicasas/genética , ADN Helicasas/fisiología , Enzimas Reparadoras del ADN/deficiencia , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/fisiología , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/fisiología , Diagnóstico Diferencial , Endonucleasas/deficiencia , Endonucleasas/genética , Endonucleasas/fisiología , Genes Recesivos , Predisposición Genética a la Enfermedad , Genotipo , Trastornos del Crecimiento/diagnóstico , Humanos , Levodopa/uso terapéutico , Mutación , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Proteínas Nucleares/fisiología , Estrés Oxidativo/genética , Fenotipo , Trastornos por Fotosensibilidad/diagnóstico , Proteínas de Unión a Poli-ADP-Ribosa , Factores de Transcripción/deficiencia , Factores de Transcripción/genética , Factores de Transcripción/fisiología , Proteína de la Xerodermia Pigmentosa del Grupo D/deficiencia , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/fisiologíaRESUMEN
A 19 moth-old child who presented seizures secondary to intractable hypoglycemia, fulfilling the clinical and biochemical criteria for hyperinsulinism was studied. Histopathological findings of the pancreas showed the presence of small clusters of b cell islets throughout acinar tissue near ducts, in both the head and the proximal third of the body. Proximal pancreatectomy (60%) and distal pancreatic-jejunostomy (Roux-in-Y) were performed. This procedure was effective in reverting hypoglycemia and constitutes the first successful alternative treatment.
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Hiperinsulinismo/etiología , Hipoglucemia/etiología , Nesidioblastosis/complicaciones , Técnicas de Diagnóstico Endocrino , Humanos , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/cirugía , Hipoglucemia/diagnóstico , Hipoglucemia/cirugía , Lactante , Masculino , Nesidioblastosis/patología , Nesidioblastosis/cirugía , Páncreas/patología , Páncreas/cirugía , Pancreatectomía/métodos , Resultado del TratamientoRESUMEN
En 1938 Laidiaw acuñó el término de nesidioblastosis refiriéndose a una neodiferenciación de los islotes de Langerhans, originada del epitelio de los conductos pancreáticos. Se presenta un caso clínico de un niño de 19 meses de edad, con convulsiones secundarias a hipoglucemia intratable. Se diagnosticó hiperinsulinismo con base en criterios clínicos y bioquímicos. Los hallazgos histopatológicos del páncreas mostraron la presencia de racimos de islotes de células P por todo el tejido acinar localizados en cabeza y un tercio proximal del cuerpo. Se realizó el diagnóstico de nesidioblastosis y para su tratamiento se practicó pancreatectomía proximal (60%), con una pancreático yeyunostomía distal (Y en Roux). Después del tratamiento, el paciente tuvo normalización de los niveles séricos de glucosa y de insulina. Se concluye que este procedimiento resultó efectivo al revertir la hipoglucemia, por lo que constituye el primer tratamiento alternativo al método convencional.
A 19 month old child who presented seizures secondary to intractable hypoglycemia, fulfilling the clinical and biochemical criteria for hyperinsulinism was studied. Histopathological findings of the pancreas showed the presence of small clusters of b cell islets throughout acinar tissue near ducts, in both the head and the proximal third of the body. Proximal pancreatectomy (60%) and distal pancreatic jejunostomy (Roux in Y) were performed. This procedure was effective in reverting hypoglycemia and constitutes the first successful alternative treatment.