Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/4785
Título: Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia
Autor: David, Susana
Aguiar, Pedro
Antunes, Liliana
Dias, Alexandra
Morais, Anabela
Sakuntabhai, Anavaj
Lavinha, João
Palavras-chave: Agentes Microbianos e Ambiente
Determinantes Imunológicos em Doenças Crónicas
Determinantes da Saúde e da Doença
Doenças Genéticas
Epidemiologia Clínica
Infecções Respiratórias
Patologias do Glóbulo Vermelho
Sickle Cellanemia
TLR2
Genetic Variants
Viral and Bacterial Infection
Hemolytic Component
Genotype-to-phenotype Association
Data: 30-Jun-2017
Editora: Springer-Verlag (Germany)
Citação: Immunogenetics. 2017 Jun 30. doi: 10.1007/s00251-017-1013-7. [Epub ahead of print]
Resumo: Sickle 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
Peer review: yes
URI: http://hdl.handle.net/10400.18/4785
DOI: 10.1007/s00251-017-1013-7
ISSN: 1432-1211
Versão do Editor: https://link.springer.com/article/10.1007%2Fs00251-017-1013-7
Aparece nas colecções:DEP - Artigos em revistas internacionais
DGH - Artigos em revistas internacionais

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