Repository logo
 
Publication

Haemolysis in sickle cell anaemia: a genotype/phenotype association study

2012-10Conference object Open access
Simple item page
dc.contributor.authorLavinha, João
dc.contributor.authorCoelho, Andreia
dc.contributor.authorDias, Alexandra
dc.contributor.authorMorais, Anabela
dc.contributor.authorFerreira, Emanuel
dc.contributor.authorPicanço, Isabel
dc.contributor.authorNunes, Baltazar
dc.contributor.authorFaustino, Paula
dc.date.accessioned2013-02-12T12:41:48Z
dc.date.available2013-02-12T12:41:48Z
dc.date.issued2012-10
dc.description.abstractSickle-cell anaemia (SCA) is a clinically heterogeneous autosomal recessive monogenic chronic anaemia characterized by recurrent episodes of severe vaso-occlusion, haemolysis and infection. Several genetic and environmental modifiers have been suggested to modulate the onset and course of SCA. As part of a wider research on the development and validation of vaso-occlusion early predictors in SCA, we have studied the association between haemolysis biomarkers (LDH, total bilirrubin and reticulocyte count) and the inheritance of genetic variants of ten candidate genes in a series of 99 paediatric SS patients (median current age of 9.9 years) followed-up in two general hospitals in Greater Lisbon area (median follow-up/patient of 5.0 years). Although in a large number of tests a seemingly significant (i.e., p<0.05) association was observed, only the following ones were confirmed upon correction for the false discovery rate: (a) An elevated LDH was associated to haplotype 7 within VCAM1 gene. (b) A lower total bilirrubin was associated to the 3.7kb deletion at HBA gene, rs2070744_T allele and haplotypes 3 and 4 at NOS3 gene and haplotype 9 within VCAM1 gene and rs3783598_G and rs3917024_T alleles at VCAM1 gene promoter. (c) A diminished reticulocyte count was associated to the 3.7kb deletion at HBA gene, whereas an elevated count was associated to rs1984112_G allele at CD36 gene. Furthermore, at the phenotypic level all three haemolysis biomarkers were positively associated to left ventricle dilation, a common chronic complication of SCA. On the whole, our findings suggest a complex genetic architecture for the haemolytic endophenotype in SCA involving multiple pathways, namely control of erythrocyte volume and haemoglobinisation, vascular cell adhesion, NO synthesis and lipid metabolism. Further mechanistic studies are needed to explore these avenues leading to a better understanding of the inter- and intra-individual clinical variability of SCA. Acknowledgement: Work partially funded by FCT grants PIC/IC/83084/2007 and CIGMH.por
dc.identifier.urihttp://hdl.handle.net/10400.18/1284
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherInstituto Nacional de Saúde Doutor Ricardo Jorge, IPpor
dc.relationFCT - PIC/IC/83084/2007 e CIGMHpor
dc.subjectSickle Cell Diseasepor
dc.subjectHemoglobinopatiaspor
dc.subjectVariante de Hemoglobinapor
dc.subjectHbSpor
dc.subjectDoenças Genéticaspor
dc.titleHaemolysis in sickle cell anaemia: a genotype/phenotype association studypor
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceTróia, Portugalpor
oaire.citation.title13º Congresso Nacional de Pediatria, Sociedade Portuguesa de Pediatria, 11-13 Outubro 2012por
rcaap.rightsopenAccesspor
rcaap.typeconferenceObjectpor

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
poster SPP Haemolysis_Poster_SPP_2013 - Final_20121003.pdf
Size:
263.69 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

DGH - Posters/abstracts em congressos nacionais
DEP - Posters/abstracts em congressos nacionais