Exploring the potential benefits of pharmacogenomics in chronic respiratory diseases.

Tweetable abstract Opportunities for pharmacogenetics implementation in chronic respiratory diseases through the employment of genotype-guided prescriptions in treating nonrespiratory comorbidities.

IL10 rs1800872 Is Associated with Non-Steroidal Anti-Inflammatory Drugs Exacerbated Respiratory Disease in Mexican-Mestizo Patients.

Non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (N-ERD) is a disease integrated by asthma, nasal polyps, and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAID). Genetic association studies have explored single nucleotide polymorphisms (SNPs) in genes involved in theoretical pathophysiological mechanisms, but most of these lack replication of findings in second populations. Our objective was to evaluate the association of SNPs in candidate genomic regions described in Asian and European subjects with N-ERD in Mexican-mestizo patients. We designed a replicative study in two stages. We included 381 SNPs selected by fine mapping of associated genes in a microarray, which were tested in three groups: N-ERD (N), asthma (A), and control group (CG); by means of GoldenGate array, positive results by genetic models were validated in the second stage in another population through qPCR with the same methodology. In the allelic model, we identified 11 SNPs in N vs. CG comparison, and five in N vs. A and A vs. CG, respectively. By genetics models, all SNPs in PPARG, rs13239058 in TBXAS1, and rs1554286 and rs1800872 in IL10 were associated in both models. In the second stage, only rs1800872CC showed an association in the dominant model comparing N vs. GC, p = 0.004, OR = 0.44. In conclusion, rs1800872 in IL10 was the only associated with N-ERD in Mexican-mestizo patients.

Personalized Medicine in Respiratory Disease: Role of Proteomics.

Respiratory diseases affect humanity globally, with chronic lung diseases (e.g., asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, among others) and lung cancer causing extensive morbidity and mortality. These conditions are highly heterogeneous and require an early diagnosis. However, initial symptoms are nonspecific, and the clinical diagnosis is made late frequently. Over the last few years, personalized medicine has emerged as a medical care approach that uses novel technology aiming to personalize treatments according to the particular patient's medical needs. This review highlights the contributions of proteomics toward the understanding of personalized medicine in respiratory disease and its potential applications in the clinic.

Fibrosis quística atípica y enfermedad del CFTR: a propósito de un caso de traqueobroncopatía osteocondroplástica / Atypical cystic fibrosis and cystc fibrosis related disease: a case of osteochondroplastic tracheobronchopathy

Cystic fibrosis (CF) is a genetic common disease within the white population, caused by mutations in the CF transmembrane conductance regulator gene (CFTR). It mainly involves progressive respiratory diseases and pancreatic exocrine insufficiency. Atypical CF represents approximately 2 percent of cases and affects adolescents or adults with pancreatic exocrine sufficiency, normal or borderline sweat chloride test, or presenting a single clinical feature, such as chronic rhinosinusitis, nasal polyposis, pancreatitis, biliary cirrhosis, portal hypertension, or obstructive azoospermia. Clinical heterogeneity depends on the amount of functional protein, which is influenced by the type of mutation. Other genes and environmental exposure could modify the phenotype. Certain conditions may result from CFTR dysfunction without fulfilling diagnostic criteria for CF: the term CFTR-related disease is used to describe a single organ disease, and in cases where a mild CF phenotype is apparent, it is called atypical CF. We describe a case of osteocondroplastic tracheobronchopaty as a form of mild presentation of atypical CF or CFTR-related disease.

La fibrosis quística (FQ), enfermedad genética frecuente de la raza blanca, es causada por la mutación del gen que codifica para la proteína reguladora de transmembrana (CFTR). Produce principalmente una enfermedad respiratoria progresiva e insuficiencia pancreática. La FQ atípica representa el 2 por ciento de los casos. Aparece en adolescentes y adultos con suficiencia pancreática, test del sudor normal o dudoso o solo un sistema afectado: sinusitis crónica, poliposis nasal, pancreatitis, cirrosis biliar, hipertensión portal o azospermia obstructiva. La heterogeneidad clínica depende de la cantidad de CFTR funcionante, la que está influenciada por el tipo de mutación. Otros genes o la exposición ambiental podrían modificar el fenotipo. Cuando existe un órgano comprometido se la ha llamado enfermedad relacionada CFTR; en casos leves es el término FQ atípica. Esta revisión describe un paciente con traqueobroncopatía osteocondroplástica como forma de presentación de FQ atípica o de enfermedad relacionada a CFTR.

Angiotensin-converting enzyme DD genotype is associated with worse perinatal cardiorespiratory adaptation in preterm infants.

OBJECTIVES: The angiotensin-converting enzyme (ACE) deletion (D) variant is associated with greater ACE activity and perhaps with deleterious cardiorespiratory pathophysiological responses. We determined whether the early health status of the preterm infant was adversely influenced by homozygosity for the D allele (DD genotype) compared with ID or II genotype. Study design Angiotensin-converting enzyme genotype was determined in a cohort of 148 preterm infants born in Bristol, United Kingdom (median gestational age, 31 weeks; range, 28-32). Intensive care data were prospectively obtained. Primary analysis was by Mann-Whitney U and chi(2) tests. RESULTS: Higher oxygen, circulatory support requirements, and base deficit in the first 12 hours after birth were found in infants with DD genotype (minimum inspired oxygen concentration in first 12 hours, median [interquartile range], DD 0.26 [0.21-0.40], ID/II 0.21 [0.21-0.30], P=.028; blood pressure support in first 12 hours, DD 12 [30%], ID/II 15 [14%], P=.039; worse base deficit in first 12 hours, DD 4.8 [7.7 to 0], ID/II 0 [5.3 to 0], P=.020). CONCLUSIONS: Angiotensin-converting enzyme polymorphism has a role in the development of preterm cardiorespiratory disease. The DD genotype, encoding higher angiotensin-converting enzyme activity, may adversely influence the early health status of preterm infants.

Genética molecular y patología II / Molecular genetics and pathology II

Las patologías genéticas humanas más frecuentes se deben a la falla de un gen único que puede alterar la estructura de una proteína importante, modificando su funcionalidad. Este cambio estructural tendrá efectos distintos según el tipo de proteína involucrada. Cada tipo de defecto parece tener un patrón propio de transmisión que permite interpretar la Genética clásica desde un punto de vista molecular. En la segunda parte de ésta revisión se explican los patrones mendelianos de herencia y se consideran algunas patologías de herencia autosómica recesiva que altera la función respiratoria. Se describen algunas excepciones a los patrones clásicos de herencia y se considera brevemente el impacto de la Genética molecular en la interpretación de las aberraciones cromosómicas, como también sus proyecciones al diagnóstico prenatal, el consejo genético y la terapia génica

Genética molecular y patología I / Molecular genetics and pathology I

La Genética estudia la herencia y la variación. Sus leyes básicas fueron establecidas por Gregor Mendel en 1865 y son el fundamento de la Genética clásica. En el siglo XX la Bioquímica ha provocado una explosión en los conocimientos de Genética. Se ha podido establecer la naturaleza química de los genes. Los mecanismos de replicación, transmisión y expresión génica. Más recientemente han podido explicarse rasgos mendelianos por mecanismos moleculares. Estos avances han modificado los conceptos clásicos de patología genética. El conocimiento de los mecanismos moleculares facilita el diagnóstico, el consejo genético y eventualmente la terapia. En la primera parte de esta revisión se describen los aspectos más elevado del genoma humano, las técnicas de estudio del material genético y como estas han influido en nuestra comprensión de la patología genética. La segunda parte trata los desórdenes monogénicos, sus mecanismos moleculares y las relaciones entre los tipos de defectos y el modo como se heredan. Cuando es posible, se toman como ejemplo desórdenes que afectan la función respiratoria. Se consideran también casos especiales que alteran los patrones mendelianos de herencia. Se revisan brevemente las aberraciones cromosónicas. Se discute brevemente el impacto de la técnicas de Biología molecular en el diagnóstico prenatal, el consejo genético y la terapia génica

Manifestaciones pulmonares de padecimientos genéticos en edad pediátrica / Pulmonary manifestations of genetic diseases in pediatrics

Se analizan los padecimientos genéticos cuya historia natural afecta primaria o secundariamente al aparato repiratorio. Con fines de asesoramiento genético, la patología se dividió en cuatro categorías: 1.Padecimiento cromosómicos, 2.Mendelianos simples, 3.De etiología multifactorial y 4.Malformaciones congénitas