Interethnic variation of the MMP-9 microsatellite in Amerindian and Mexican Mestizo populations: considerations for genetic association studies.

We studied the interethnic variation of the MMP-9 microsatellite in the Mestizo and Amerindian populations using blood samples collected from 435 healthy unrelated individuals from the Central Valley of Mexico. DNA samples were genotyped using the -90 (CA)12-27 repeat near the MMP transcriptional start site using capillary electrophoresis. Our data were compared with those from African, Asian, and European populations (N = 729). Both Mestizo and Amerindian populations were in Hardy-Weinberg equilibrium (P ≥ 0.05). However, strong genetic heterogeneity was found within the Mestizo population (94%, P ≤ 0.0001), which exhibited the highest frequency of Amerindian, African, and European alleles. Likewise, Amerindians showed 6.7% variation among populations (P ≤ 0.0001), suggesting a genetic substructure potentially associated with linguistic affiliations. These findings were corroborated with principal component and population differentiation analyses, which showed relative proximity among the Mestizos and their historical parental populations: Asian (FST ≥ 0.05), European (FST ≥ 0.09), and African (FST ≥ 0.02). Nevertheless, important differences were found between Mestizo and Nahuas (P ≤ 0.0001), and between Mestizo and Me'Phaas (P ≤ 0.0001). These findings highlight the importance of determining local-specific patterns to establish the population variability of MMP-9 and other polymorphic markers. Validation of candidate markers is critical to identifying risk factors; however, this depends on knowledge of population genetic variation, which increases the possibility of finding true causative variants. We also show that dissimilar ethnic backgrounds might lead to spurious associations. Our study provides useful considerations for greater accuracy and robustness in future genetic association studies.

Analysis of the genotypic diversity of strains of Helicobacter pylori isolated from pediatric patients in Mexico.

Genotypic differences in Helicobacter pylori play an important role in infection. We characterized the diversity of the cagA, cagE, babA2, and vacA genes in H. pylori strains isolated from pediatric patients and the relationship between these genes and clinical disease. Additionally, we employed the Neighbor-net algorithm to predict the behavior of the genotypes of the strains isolated from patients. Of 93 patients analyzed, 32 were positive for infection. A total of 160 H. pylori strains (five isolates per positive patient) were analyzed. A total of 91% and 83% of strains possessed the cagA and cagE genes, respectively. For the vacA gene, 84% of strains possessed the s1 allele, 15% the s2 allele, 81% the m1 allele and 13.8% the m2 allele. The babA2 gene was present in 79% of strains. Infection with H. pylori strains with the vacA (s1m1) genotype was associated with risk of esophagitis and gastritis (p=0.0001). The combination of cagA and vacA (s1m1) was significantly associated with abdominal pain (p=0.002); however, EPIYA type was not significantly associated with abdominal pain. A total of 16 different genotypes were identified; the most common genotype was vacAs1m1cagA+cagE+babA2+ (47.5%). A total of 84% of pediatric patients were infected by at least two and up to five different genotypes. The network recovered two genotype groups (A: strains with vacAs1 and B: strains with vacAs2). The presence of multiple paths in the network suggests that reticulate events, such as recombination or reinfection, have contributed to the observed genotypic diversity.

Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia.

BACKGROUND: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). METHODS: A case-control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. RESULTS: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47-11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20-0.91). CONCLUSION: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS.

Normal development of the muscular region of the interventricular septum. II. The importance of myocardial proliferation.

In a first paper, we concluded that the muscular region of the interventricular septum is developed by the trabecular branches and showed evidence that the developing interventricular septum elongates in a direction opposite to that of atria. Nevertheless, to date the literature is lacking precise information on the importance of myocardial proliferation not only in this process but also in the morphogenesis of the ventricular cavities. The aim of this study was to determine the spatial and temporal distribution of high-intensity foci of cycling myocytes in the ventricular region of the heart of chicken embryos during cardiac septation. Histological studies, detection of the proliferating cell nuclear antigen by light and confocal microscopy and flow cytometric analysis were carried out. The results corroborate that the developing interventricular septum grows in a direction opposite to that of atria. A remoulding mechanism that results in fenestrated trabecular sheets and trabecular branching is discussed. Our findings allowed us to summarize the normal morphogenesis of the muscular region of the interventricular septum in a way that is different from that suggested by other researchers.