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Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia

2017-06-30Journal article Restricted access
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dc.contributor.authorDavid, Susana
dc.contributor.authorAguiar, Pedro
dc.contributor.authorAntunes, Liliana
dc.contributor.authorDias, Alexandra
dc.contributor.authorMorais, Anabela
dc.contributor.authorSakuntabhai, Anavaj
dc.contributor.authorLavinha, João
dc.date.accessioned2017-08-02T11:01:51Z
dc.date.available2018-06-30T00:30:12Z
dc.date.issued2017-06-30
dc.description.abstractSickle 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 patientspt_PT
dc.description.sponsorshipThis study was carried out with financial support from FCT/MEC through national funds and cofinanced by FEDER, under the Partnership Agreement PT2020, in the project with reference UIDMULTI/00211/2013, and was partially funded by FCT grants PIC/IC/83084/2007 and the Centro de Investigação em Genética Molecular Humana (CIGMH).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationImmunogenetics. 2018 Jan;70(1):37-51. doi: 10.1007/s00251-017-1013-7. Epub 2017 Jun 30.pt_PT
dc.identifier.doi10.1007/s00251-017-1013-7pt_PT
dc.identifier.issn1432-1211
dc.identifier.otherESSN: 0093-7711
dc.identifier.urihttp://hdl.handle.net/10400.18/4785
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer-Verlag (Germany)pt_PT
dc.relationDEVELOPMENT AND VALIDATION OF VASO-OCCLUSION EARLY PREDICTORS IN A MENDELIAN MODEL OF VASCULAR DISEASE
dc.relation.publisherversionhttps://link.springer.com/article/10.1007%2Fs00251-017-1013-7pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAgentes Microbianos e Ambientept_PT
dc.subjectDeterminantes Imunológicos em Doenças Crónicaspt_PT
dc.subjectDeterminantes da Saúde e da Doençapt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectEpidemiologia Clínicapt_PT
dc.subjectInfecções Respiratóriaspt_PT
dc.subjectPatologias do Glóbulo Vermelhopt_PT
dc.subjectSickle Cellanemiapt_PT
dc.subjectTLR2pt_PT
dc.subjectGenetic Variantspt_PT
dc.subjectViral and Bacterial Infectionpt_PT
dc.subjectHemolytic Componentpt_PT
dc.subjectGenotype-to-phenotype Associationpt_PT
dc.titleVariants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDEVELOPMENT AND VALIDATION OF VASO-OCCLUSION EARLY PREDICTORS IN A MENDELIAN MODEL OF VASCULAR DISEASE
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5646-ICCMS/PIC%2FIC%2F83084%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F00211%2F2013/PT
oaire.citation.endPage15pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleImmunogeneticspt_PT
oaire.fundingStream5646-ICCMS
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication466fa8ec-15ed-4907-9ca9-5fc5c0916fc4
relation.isProjectOfPublication4641127c-7dd5-44f4-a3d1-d3c4d744ba51
relation.isProjectOfPublication.latestForDiscovery4641127c-7dd5-44f4-a3d1-d3c4d744ba51

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