Cox, Sharon E. ORCID: https://orcid.org/0000-0002-9908-2936, Makani, Julie ORCID: https://orcid.org/0000-0002-4801-6250, Soka, Deogratias, L'Esperence, Veline S., Kija, Edward, Dominguez Salas, Paula ORCID: https://orcid.org/0000-0001-8753-4221, Newton, Charles R. J., Birch, Anthony A., Prentice, Andrew M. and Kirkham, Fenella J. (2014) Haptoglobin, alpha‐thalassaemia and glucose‐6‐phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania. British Journal of Haematology, 165 (5). pp. 699-706. ISSN 0007-1048 (Print), 1365-2141 (Online) (doi:10.1111/bjh.12791)

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Abstract

Transcranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv) of basal intracranial vessels and is used clinically to detect stroke risk in children with sickle cell anaemia (SCA). Co-inheritance in SCA of alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) polymorphisms is reported to associate with high CBFv and/or risk of stroke. The effect of a common functional polymorphism of haptoglobin (HP) is unknown. We investigated the effect of co-inheritance of these polymorphisms on CBFv in 601 stroke-free Tanzanian SCA patients aged <24 years. Homozygosity for alpha-thalassaemia 3·7 deletion was significantly associated with reduced mean CBFv compared to wild-type (β-coefficient −16·1 cm/s, P = 0·002) adjusted for age and survey year. Inheritance of 1 or 2 alpha-thalassaemia deletions was associated with decreased risk of abnormally high CBFv, compared to published data from Kenyan healthy control children (Relative risk ratio [RRR] = 0·53 [95% confidence interval (CI):0·35–0·8] & RRR = 0·43 [95% CI:0·23–0·78]), and reduced risk of abnormally low CBFv for 1 deletion only (RRR = 0·38 [95% CI:0·17–0·83]). No effects were observed for G6PD or HP polymorphisms. This is the first report of the effects of co-inheritance of common polymorphisms, including the HP polymorphism, on CBFv in SCA patients resident in Africa and confirms the importance of alpha-thalassaemia in reducing risk of abnormal CBFv.

Item Type:	Article
Uncontrolled Keywords:	Tanzania, sickle cell anaemia, sickle cell disease, Africa, children, cerebral blood flow velocity
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science > Natural Resources Institute > FaNSI - Food Systems for Improved Nutrition Faculty of Engineering & Science Faculty of Engineering & Science > Natural Resources Institute
Related URLs:	Publisher Publisher
Last Modified:	09 Sep 2021 11:30
URI:	http://gala.gre.ac.uk/id/eprint/33792

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