RESUMO
The so-called tumor necrosis factor (TNF) block includes the TNFA, lymphotoxin alpha and beta (LTA and LTB) genes with single-nucleotide polymorphisms (SNP) and microsatellites with an allele frequency that exhibits interpopulation variability. To date, no reports have included both SNPs and microsatellites at the TNF block to study Mestizo or Amerindian populations from Mexico. In this study, samples of five Mexican Mestizo populations (Durango, Guadalajara, Monterrey, Puebla, and Tierra Blanca) and four native-Mexican populations (North Lacandonians, South Lacandonians, Tepehuanos, and Yaquis) were genotyped for two SNPs (LTA+252A>G and TNFA-308G>A) and four microsatellites (TNFa, d, e, and f), to analyze the genetic substructure of the Mexican population. Allele and haplotype frequencies, linkage disequilibrium (LD), and interpopulation genetic relationships were calculated. There was significant LD along almost all of the TNF block but the lowest D' values were observed for the TNFf-TNFd pair. Mestizos showed higher allele and haplotype diversity than did natives. The genetic differentiation level was reduced among Mestizos; however, a slightly, but significant genetic substructure was observed between northern and southern Mexican Mestizos. Among the Amerindian populations, the genetic differentiation level was significantly elevated, particularly in both North and South Lacandonians. Furthermore, among Southern Lacandonians, inhabitants of Lacanja town were the most differentiated from all the Mexicans analyzed. The data presented here will serve as a reference for further population and epidemiological studies including these TNF polymorphisms in the Mexican population.
Assuntos
Haplótipos , Indígenas Norte-Americanos/genética , Desequilíbrio de Ligação , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Feminino , Humanos , Masculino , MéxicoRESUMO
In previous studies in animal models, Trypanosoma cruzi-induced oxidative stress and damage have sometimes been controlled by the host's anti-oxidant defence responses. The role of the anti-oxidant defence responses, such as the activities of the anti-oxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD), in protection against inflammation and damage have now been investigated in humans infected with T. cruzi. The subjects were 32 asymptomatic but seropositive individuals with the indeterminate form of Chagas disease, 18 symptomatic and seropositive patients with the chronic disease, and 50 seronegative and apparently healthy controls. The inflammatory process was explored using serum concentrations of tumour necrosis factor (TNF) and NO. The serum concentrations of GPx in the patients in the indeterminate phase of infection were similar to those in the controls but much higher than those in the chronic cases (P=0.001). The serum concentrations of SOD in the patients in the indeterminate phase of infection were not only significantly higher than those in the cases of chronic Chagas disease (P=0.0004) but also significantly higher than those in the controls (P<0.001). The seropositive subjects had significantly higher serum concentrations of TNF and NO than the controls (P<0.01 for each) and the cases of chronic Chagas disease had significantly higher serum concentrations of TNF and NO than the subjects with the indeterminate form of the disease (P<0.01 for each). It therefore appears that the host's anti-oxidant defence responses (at least in terms of elevated concentrations of SOD) may inhibit inflammation during the indeterminate phase of Chagas disease.