CHRM2 but not CHRM1 or CHRM3 polymorphisms are associated with asthma susceptibility in Mexican patients.

Asthma is a complex disease for which genetic predisposition has been widely documented. Considerable evidence supports the hypothesis that polymorphisms in the muscarinic-cholinergic (CHRM) genes could be involved in asthma pathogenesis, bronchial hyperresponsiveness, and mucus secretion. To determine whether single nucleotide polymorphisms (SNPs) or haplotypes in CHRM1, CHRM2, or CHRM3 are associated with asthma in Mexican pediatric population. We performed a case-control study including 398 pediatric cases with asthma and 450 healthy controls. We analyzed 19 SNPs distributed among these three genes. Two of the seven SNPs located in CHRM2, the 3' untranslated region rs8191992 and rs6962027, differed significantly in allele frequencies between patients with asthma and healthy controls [odds ratio (OR) 1.42, 95 % confidence interval (95 % CI) 1.14-1.77, P = 0.001, and OR 1.50, 95 % CI 1.21-1.87, P = 0.0002, respectively]. Statistical significance remained after multiple comparison corrections (P = 0.003 and P = 0.005, respectively). The haplotypes AA and TT, containing both major and minor alleles from rs8191992 and rs6962027, also differed between cases and controls. The haplotype AA occurred at a lower frequency in cases (OR 0.67, 95 % CI 0.53-0.85, P = 0.001) whereas the haplotype TT was overrepresented in cases compared to controls (28 vs 21 %, respectively; OR 1.46, 95 % CI 1.15-1.85, P = 0.002). No association was observed between CHRM1 or CHRM3 SNPs or haplotypes and asthma. CHRM2 polymorphisms are implicated in the genetic etiology of asthma.

[Genotyping and its applications, a look to the future]. / Genotipificación y sus aplicaciones, una mirada hacia el futuro.

The detection of the most significant erythrocyte antigens present in each one of the individuals is fundamental when carrying out a transfusion or a transplant. Detection to date is performed by conventional serological methods through the antigen-antibody reaction. But several drawbacks may arise depending on the pathology under study, limiting the availability of blood components. Molecular methods such as genotyping is a tool that complements sensitivity and specificity and has come to revolutionize immunohematology in the blood bank, allowing not only the detection of erythrocyte antigens but also platelet antigens. These methodologies are applicable in patients and in large-scale donors, starting from the allelic variants present in each of the genes that code for the antigens of clinical interest, using microarray systems or systems based on particles labeled with specific probes or their variants that allow an analysis from the immunohematological point of view.

La detección de los antígenos eritrocitarios más significativos presentes en cada uno de los individuos es fundamental cuando se lleva a cabo una transfusión o un trasplante. La detección a la fecha se realiza mediante métodos serológicos convencionales a través de la reacción de antígeno-anticuerpo. Pero se pueden presentar varios inconvenientes dependiendo de la patología en estudio, lo cual limita la disponibilidad de los hemocomponentes. Los métodos moleculares, como la genotipificación, son una herramienta que complementa la sensibilidad y especificidad y que han venido a revolucionar la inmunohematología en el banco de sangre, lo cual permite no solo la detención de antígenos eritrocitarios sino también la de antígenos plaquetarios. Estas metodologías son aplicables en pacientes y en donantes a gran escala, partiendo de las variantes alélicas presentes en cada uno de los genes que codifican para los antígenos de interés clínico, utilizando los sistemas de microarreglos o los sistemas basados en partículas marcadas con sondas específicas o sus variantes que permiten un análisis desde el punto de vista inmunohematológico.

Trypanosoma cruzi: seroprevalence detected in the blood bank of the Instituto Nacional de Pediatría, Mexico City, in the period 2004 through 2009.

BACKGROUND: The second most common mode of Trypanosoma cruzi or Chagas disease transmission is via therapeutic blood transfusion. In Mexico, control of T. cruzi is still in its initial phase; in fact, there are only 14 studies published covering 10 states on T. cruzi seroprevalence in donated blood in Mexico. Here we present the results of 5 years of trypanosomiasis screening in the blood bank of the Instituto Nacional de Pediatría. STUDY DESIGN AND METHODS: Samples from all blood donated in the period from 2004 to 2009 were analyzed. We screened for T. cruzi using an enzyme-linked immunosorbent assay technique. Seropositive samples were then processed using the polymerase chain reaction (PCR) to detect a nuclear gene segment. RESULTS: A total of 37,333 samples were analyzed and a 0.17% (64 samples) T. cruzi seroprevalence was found. Donors were mostly from Mexico State and Mexico City, which is considered nonendemic for T. cruzi area. Of 64 seropositive samples, only two tested positive by PCR (3.12%), which amplified a 189-bp product from nuclear gene from the parasite. CONCLUSION: Although the seroprevalence of T. cruzi infection was low, this surveillance program prevented the infection of more than 100 children because each unit of blood provides 2.6 to 3.5 blood products. The majority of the donors were from Mexico State and Mexico City, which is a nonendemic area. The serodetection of T. cruzi in this region is evidence that is necessary to increase our understanding of its distribution in the Mexico City and surrounding places.

Tumor necrosis factor-alpha is a common genetic risk factor for asthma, juvenile rheumatoid arthritis, and systemic lupus erythematosus in a Mexican pediatric population.

There is a great deal of evidence that points to the association of the tumor necrosis factor-alpha (TNF-alpha) gene as a common genetic factor in the pathogenesis of diseases that are caused by inflammatory and/or autoimmune etiologies. Two single nucleotide polymorphisms (SNPs) identified in the TNF-alpha promoter region have been associated with disease susceptibility and severity. We investigated whether -308G/A and -238G/A TNF-alpha polymorphisms were associated with asthma, systemic lupus erythematosus (SLE), and juvenile rheumatoid arthritis (JRA) in a pediatric Mexican population. In a case-control study of 725 patients (asthma: 226, JRA: 171, and SLE: 328) and 400 control subjects, the participants were analyzed using the allelic discrimination technique. The genotype distribution of both TNF-alpha polymorphisms was in Hardy-Weinberg equilibrium in each group. However, there were significant differences in the allele frequency of TNF-alpha-308A between the patients and the healthy controls. This allele was detected in 2.9% of the controls, 6.0% of asthmatic and JRA patients (p = 0.002 and p = 0.0086), and 6.7% of SLE patients (p = 0.00049); statistical significance was maintained after ancestry stratification (asthma: p = 0.0143, JRA: p = 0.0083, and SLE: p = 0.0026). Stratification by gender showed that the risk for the -308A allele in asthma and JRA was greater in females (OR = 4.16, p = 0.0008 and OR = 4.4, p = 0.0002, respectively). The TNF-alpha -238A allele showed an association only with JRA in males (OR = 2.89, p = 0.004). These results support the concept that the TNF-alpha gene is a genetic risk factor for asthma, SLE, and JRA in the pediatric Mexican population.