RESUMO
Macrophage migration inhibitory factor (MIF) is an upstream proinflammatory cytokine encoded by a functionally polymorphic locus. This study of 119 patients explored the potential relationship between MIF genotype and invasive Streptococcus pneumoniae infections. We observed an association between a high-expression MIF allele and occurrence of pneumococcal meningitis.
Assuntos
Predisposição Genética para Doença/genética , Fatores Inibidores da Migração de Macrófagos/genética , Meningite Pneumocócica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Meningite Pneumocócica/microbiologia , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Fatores de Risco , Análise de Sequência de DNA , Adulto JovemRESUMO
Microsatellite repeat and single nucleotide polymorphisms (SNPs) are abundant sources of genetic variation, but existing methodologies cannot simultaneously detect these variants in a facile or inexpensive way. We describe herein a thin-film biosensor chip based on an allele-discriminating oligonucleotide array that enables genotyping for both microsatellite repeats and SNPs in a single analysis. We validated this methodology for the functionally polymorphic -794 CATT(5-8) repeat and -173 G/C SNP present in the promoter of the human gene for macrophage migration inhibitory factor (MIF). In a comparison of 30 samples collected at a rural hospital in Zambia, we observed a 100% concordance for both the CATT repeat and G/C SNP between the biosensor methodology and the conventional capillary electrophoresis. The biosensor chips are low in cost and once printed, they are robust and require no instrumentation for analysis. When combined with multiple displacement amplification, this methodology can be utilized in primitive settings for the genotyping of nanogram quantities of DNA present in blood, dried and stored on filter paper samples. We applied this methodology to a field study of MIF genotype in children with malaria, and provide first evidence for a potential association between MIF alleles and malaria infection. We also present data supporting significant population stratification of the low- versus high-expression forms of MIF that may bear on the role of this gene in infectious diseases.
Assuntos
Técnicas Biossensoriais/métodos , Fatores Inibidores da Migração de Macrófagos/genética , Repetições de Microssatélites , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Polimorfismo de Nucleotídeo Único , Saúde da População Rural , Criança , Frequência do Gene , Humanos , Malária/genética , Regiões Promotoras GenéticasRESUMO
To determine the prevalence of endoparasites and their association with diarrhea, a survey was conducted in the Southern Province of Zambia that used conventional and molecular techniques applied to stool and urine samples from school-age children (n = 93). Almost half of the stools (49.5%) were diarrhetic. The overall prevalence of Endolimax nana, Schistosoma haematobium, Blastocystis hominis, Giardia lamblia, Cryptosporidium parvum, Encephalitozoon intestinalis, and Strongyloides stercoralis was 64.3, 59.1, 53.8, 19.4, 8.6, 8.6, and 1.1%, respectively. Only the associations between infection with B. hominis and E. nana with diarrhea were statistically significant. Although B. hominis and E. nana are considered to be nonpathogenic organisms, this study demonstrated that they can be associated with diarrhea in children when they occur at high prevalence and intensity. This survey supports the recent evidence that B. hominis and E. nana infections are associated with deficient sanitation and low hygiene standards and can contribute to diarrhea in children in developing countries.