Publication
Haemolysis in sickle cell anaemia: a genotype/phenotype association study
| dc.contributor.author | Coelho, Andreia | |
| dc.contributor.author | Dias, Alexandra | |
| dc.contributor.author | Morais, Anabela | |
| dc.contributor.author | Nunes, Baltazar | |
| dc.contributor.author | Ferreira, Emanuel | |
| dc.contributor.author | Picanço, Isabel | |
| dc.contributor.author | Faustino, Paula | |
| dc.contributor.author | Lavinha, João | |
| dc.date.accessioned | 2014-12-03T18:00:26Z | |
| dc.date.available | 2014-12-03T18:00:26Z | |
| dc.date.issued | 2014-11 | |
| dc.description.abstract | Introduction: Sickle cell anaemia (SCA) is a clinically heterogeneous autosomal recessive monogenic anaemia characterised by chronic haemolysis and recurrent episodes of severe vaso-occlusion and infection. Several environmental and genetic determinants have been suggested to modulate the onset, course and outcome of SCA. The level of chronic haemolysis has been considered a critical measure of SCA severity and a possible proximate cause of some disease complications such as stroke, pulmonary hypertension, priapism, leg ulceration and cholelithiasis. Thus, we proposed to search for genetic modifiers of this sub-phenotype and gain insights into the underlying mechanisms. Patients and Methods: We studied the association between commonly measured haemolysis biomarkers (LDH, total bilirubin and reticulocyte count) and the inheritance of 41 genetic variants (34 SNP, 6 indel, 1 STR) of 10 candidate genes in a longitudinally observed series of 99 paediatric homozygous SCA patients (median current age of 9.9 yr) followed up in two general hospitals in Greater Lisboa area (median follow-up per patient of 5.0 yr). Candidate gene genotyping was performed by PCR-RFLP, Sanger sequencing, Gene Scan or Gap-PCR. All genotype distributions were tested for adherence to the Hardy-Weinberg equilibrium. When appropriate, haplotypes were inferred by software PHASE, version 2.1.1 Results: Although in a large number of tests seemingly significant association was observed only the following ones were confirmed upon correction for multiple comparisons: i) an increased serum LDH level was associated with haplotype 7 within VCAM1 gene; ii) a lower total bilirubin was associated with the 3.7-kb deletion at HBA gene, rs2070744_T allele at NOS3 gene, and haplotype 9 within VCAM1 promoter; and iii) a diminished reticulocyte count was associated with the 3.7-kb deletion at HBA, whereas an increased count was associated with rs1984112_G allele at CD36 gene. Conclusion: On the whole, our findings suggest a complex genetic architecture for the SCA haemolysis process involving multiple pathways, namely control of vascular cell adhesion, NO synthesis and erythrocyte volume and haemoglobinisation. | por |
| dc.description.sponsorship | Partially funded by FCT: PIC/IC/83084/2007 and PEst-OE/SAU/UI0009/2011 | por |
| dc.identifier.uri | http://hdl.handle.net/10400.18/2510 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.relation | DEVELOPMENT AND VALIDATION OF VASO-OCCLUSION EARLY PREDICTORS IN A MENDELIAN MODEL OF VASCULAR DISEASE | |
| dc.subject | Doenças Genéticas | por |
| dc.subject | Drepanocitose | por |
| dc.subject | Estudos de Associação | por |
| dc.subject | Variantes Genéticas | por |
| dc.subject | Hemólise | por |
| dc.title | Haemolysis in sickle cell anaemia: a genotype/phenotype association study | por |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | DEVELOPMENT AND VALIDATION OF VASO-OCCLUSION EARLY PREDICTORS IN A MENDELIAN MODEL OF VASCULAR DISEASE | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/5646-ICCMS/PIC%2FIC%2F83084%2F2007/PT | |
| oaire.citation.conferencePlace | Lisboa, Portugal | por |
| oaire.citation.title | 18ª Reunião da Sociedade Portuguesa de Genética Humana, Faculdade de Medicina de Lisboa, 9-21 novembro 2014 | por |
| oaire.fundingStream | 5646-ICCMS | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | openAccess | por |
| rcaap.type | conferenceObject | por |
| relation.isProjectOfPublication | 466fa8ec-15ed-4907-9ca9-5fc5c0916fc4 | |
| relation.isProjectOfPublication.latestForDiscovery | 466fa8ec-15ed-4907-9ca9-5fc5c0916fc4 |