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  • Genetic variation in CD36, HBA, NOS3

Genetic variation in CD36, HBA, NOS3< and VCAM1 is associated to chronic haemolysis level in sickle cell anaemia: a longitudinal study

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Published:25th Mar 2020

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 years) followed-up in two general hospitals in Greater Lisboa 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, the following ones were confirmed upon correction for multiple comparisons: (i) an elevated serum LDH was associated to haplotype 7 within VCAM1 gene; (ii) a lower total bilirubin was associated to the 3.7kb deletion at HBA gene, rs2070744_T allele at NOS3 gene, and haplotype 9 within VCAM1 promoter; and (iii) a diminished reticulocyte count was associated to the 3.7kb deletion at HBA, whereas an elevated count was associated to rs1984112_G allele at CD36 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.


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