Browsing by Author "Sakuntabhai, Anavaj"
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- Variantes na região não codificante do gene TLR2 associadas à infeção bacteriana grave na anemia falciforme pediátricaPublication . David, Susana; Aguiar, Pedro; Antunes, Liliana; Dias, Alexandra; Morais, Anabela; Sakuntabhai, Anavaj; Lavinha, JoãoA anemia falciforme é caracterizada por hemólise crónica, crises vaso- -oclusivas (CVO) e infeções recorrentes frequentemente graves. Uma coorte de 95 doentes pediátricos com anemia falciforme foi estudada quanto à associação genótipo-fenótipo para o subfenótipo “infeção bacteriana grave pelo menos uma vez durante o período de acompanhamento do doente” e três regiões polimórficas não codificantes do gene TLR2, a saber, a indel -196 a -174, o SNP rs4696480 e uma repetição em tandem (GT) n. A ausência do haplótipo [Del] -T- [n≥17] (Hap7) em homozigotia parece proteger contra a infeção bacteriana grave, numa associação estatisticamente significativa, resistindo à correção para testes múltiplos. Além disso, uma redução na taxa de incidência da infeção bacteriana grave foi associada a um aumento do componente hemolítico, aos níveis de hemoglobina fetal (antes do tratamento pela hidroxiureia) e à prevalência da alfa-talassemia de 3,7 kb. Estes resultados poderão vir a ter implicações práticas nas estratégias de cuidados de saúde para reduzir a morbilidade e mortalidade dos doentes com anemia falciforme.
- Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemiaPublication . David, Susana; Aguiar, Pedro; Antunes, Liliana; Dias, Alexandra; Morais, Anabela; Sakuntabhai, Anavaj; Lavinha, JoãoSickle cell anemia (SCA) is characterized by chronic hemolysis, severe vasoocclusive crises (VOCs), and recurrent often severe infections. A cohort of 95 SCA pediatric patients was the background for genotype-to-phenotype association of the patient's infectious disease phenotype and three non-coding polymorphic regions of the TLR2 gene, the -196 to -174 indel, SNP rs4696480, and a (GT)n short tandem repeat. The infectious subphenotypes included (A) recurrent respiratory infections and (B) severe bacterial infection at least once during the patient's follow-up. The absence of the haplotype [Del]-T-[n ≥ 17] (Hap7) in homozygocity protected against subphenotype (B), in a statistically significant association, resisting correction for multiple testing. For the individual loci, the same association tendencies were observed as in the haplotype, including a deleterious association between the SNP rs4696480 T allele and subphenotype (A), whereas the A/A genotype was protective, and a deleterious effect of the A/T genotype with subphenotype (B), as well as including the protective effect of -196 to -174 insert (Ins) and deleterious effect of the deletion (Del) in homozygocity, against subphenotype (B). Moreover, a reduction in the incidence rate of severe bacterial infection was associated to a rise in the hemolytic score, fetal hemoglobin levels (prior to hydroxyurea treatment), and 3.7-kb alpha-thalassemia. Interestingly, differences between the effects of the two latter covariables favoring a reduction in the incidence rate of subphenotype (B) contrast with a resulting increase in relation to subphenotype (A). These results could have practical implications in health care strategies to lower the morbidity and mortality of SCA patients