Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/1284
Título: Haemolysis in sickle cell anaemia: a genotype/phenotype association study
Autor: Lavinha, João
Coelho, Andreia
Dias, Alexandra
Morais, Anabela
Ferreira, Emanuel
Picanço, Isabel
Nunes, Baltazar
Faustino, Paula
Palavras-chave: Sickle Cell Disease
Variante de Hemoglobina
Doenças Genéticas
Data: Out-2012
Editora: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Resumo: Sickle-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.
Peer review: yes
URI: http://hdl.handle.net/10400.18/1284
Aparece nas colecções:DEP - Posters/abstracts em congressos nacionais
DGH - Posters/abstracts em congressos nacionais

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