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Genetic variation in CD 36 , HBA , NOS 3 and VCAM 1 is associated with chronic haemolysis level in sickle cell anaemia: a longitudinal study
Author(s) -
Coelho Andreia,
Dias Alexandra,
Morais Anabela,
Nunes Baltazar,
Ferreira Emanuel,
Picanço Isabel,
Faustino Paula,
Lavinha João
Publication year - 2014
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12226
Subject(s) - haemolysis , reticulocyte , hemolysis , allele , biology , immunology , bilirubin , gene , medicine , microbiology and biotechnology , genetics , endocrinology , messenger rna
Chronic haemolysis stands out as one of the hallmarks of sickle cell anaemia, a clinically heterogeneous autosomal recessive monogenic anaemia. However, the genetic architecture of this sub‐phenotype is still poorly understood. Here, we report the results of an association study between haemolysis biomarkers (serum LDH , total bilirubin and reticulocyte count) and the inheritance of 41 genetic variants of ten candidate genes in a series of 99 paediatric SS patients (median current age of 9.9 yr) followed up in two general hospitals in G reater L isboa area (median follow‐up per patient of 5.0 yr). Although in a large number of tests a seemingly significant (i.e. P < 0.05) association was observed, the following ones were confirmed upon correction for multiple comparisons: (i) an increased serum LDH level was associated with haplotype 7 within VCAM 1 gene; (ii) a lower total bilirubin was associated with the 3.7‐kb deletion at HBA gene, rs2070744_T allele at NOS 3 gene, and haplotype 9 within VCAM 1 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 CD 36 gene. On the whole, our findings suggest a complex genetic architecture for the sickle cell anaemia haemolysis process involving multiple pathways, namely control of vascular cell adhesion, NO synthesis and erythrocyte volume and haemoglobinisation.