Publication
Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia
| dc.contributor.author | David, S | |
| dc.contributor.author | Aguiar, P | |
| dc.contributor.author | Antunes, L | |
| dc.contributor.author | Dias, A | |
| dc.contributor.author | Morais, A | |
| dc.contributor.author | Sakuntabhai, A | |
| dc.contributor.author | Lavinha, J | |
| dc.date.accessioned | 2018-04-12T15:22:13Z | |
| dc.date.available | 2018-04-12T15:22:13Z | |
| dc.date.issued | 2018 | |
| dc.description.abstract | 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. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Immunogenetics. 2018 Jan;70(1):37-5 | pt_PT |
| dc.identifier.doi | 10.1007/s00251-017-1013-7 | pt_PT |
| dc.identifier.issn | 1432-1211 | |
| dc.identifier.uri | http://hdl.handle.net/10400.10/1988 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Springer Verlag | pt_PT |
| dc.subject | Sickle cell anemia | pt_PT |
| dc.title | Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | New York | pt_PT |
| oaire.citation.title | Immunogenetics | pt_PT |
| rcaap.rights | closedAccess | pt_PT |
| rcaap.type | article | pt_PT |