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Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania

Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania
Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania

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.

Adolescent, Anemia, Sickle Cell, Blood Flow Velocity, Cerebrovascular Circulation, Child, Child, Preschool, Epistasis, Genetic, Female, Gene Deletion, Genotype, Glucosephosphate Dehydrogenase, Haptoglobins, Homozygote, Humans, Infant, Male, Polymorphism, Single Nucleotide, Risk Factors, Ultrasonography, Doppler, Transcranial, Young Adult, alpha-Thalassemia, Journal Article, Research Support, Non-U.S. Gov't
0007-1048
699-706
Cox, Sharon E.
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Makani, Julie
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Soka, Deogratias
493329a2-35e6-4fce-9402-bcfe516ab775
L'Esperence, Veline S.
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Kija, Edward
d38d0994-353f-4fd2-a5e0-5c102ba89a37
Dominguez-Salas, Paula
ca7c5cfb-603f-4851-af0e-e64548b0400f
Newton, Charles R.J.
efad95f0-8647-440e-aeae-527f30d0cac7
Birch, Anthony A.
755f2236-4c0c-49b5-9884-de4021acd42d
Prentice, Andrew M.
6b851f61-f989-48f6-8109-9a7408254728
Kirkham, Fenella J.
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58
Cox, Sharon E.
40718807-416d-47df-a663-18df62802590
Makani, Julie
76a145a7-02fc-43ea-a1df-3a52d2004e48
Soka, Deogratias
493329a2-35e6-4fce-9402-bcfe516ab775
L'Esperence, Veline S.
b58047d4-e5a6-4f86-9d57-d568151deccd
Kija, Edward
d38d0994-353f-4fd2-a5e0-5c102ba89a37
Dominguez-Salas, Paula
ca7c5cfb-603f-4851-af0e-e64548b0400f
Newton, Charles R.J.
efad95f0-8647-440e-aeae-527f30d0cac7
Birch, Anthony A.
755f2236-4c0c-49b5-9884-de4021acd42d
Prentice, Andrew M.
6b851f61-f989-48f6-8109-9a7408254728
Kirkham, Fenella J.
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58

Cox, Sharon E., Makani, Julie, Soka, Deogratias, L'Esperence, Veline S., Kija, Edward, Dominguez-Salas, Paula, 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), 699-706. (doi:10.1111/bjh.12791).

Record type: Article

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.

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Accepted/In Press date: 5 January 2014
e-pub ahead of print date: 21 February 2014
Published date: June 2014
Additional Information: © 2014 The Authors. British Journal of Haematology Published by John Wiley & Sons Ltd.
Keywords: Adolescent, Anemia, Sickle Cell, Blood Flow Velocity, Cerebrovascular Circulation, Child, Child, Preschool, Epistasis, Genetic, Female, Gene Deletion, Genotype, Glucosephosphate Dehydrogenase, Haptoglobins, Homozygote, Humans, Infant, Male, Polymorphism, Single Nucleotide, Risk Factors, Ultrasonography, Doppler, Transcranial, Young Adult, alpha-Thalassemia, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 419541
URI: https://eprints.soton.ac.uk/id/eprint/419541
ISSN: 0007-1048
PURE UUID: 5aff6a67-37ab-4e38-85c3-8c10bff75053
ORCID for Anthony A. Birch: ORCID iD orcid.org/0000-0002-2328-702X
ORCID for Fenella J. Kirkham: ORCID iD orcid.org/0000-0002-2443-7958

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Date deposited: 13 Apr 2018 16:30
Last modified: 13 Jun 2019 00:37

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Contributors

Author: Sharon E. Cox
Author: Julie Makani
Author: Deogratias Soka
Author: Veline S. L'Esperence
Author: Edward Kija
Author: Paula Dominguez-Salas
Author: Charles R.J. Newton
Author: Anthony A. Birch ORCID iD
Author: Andrew M. Prentice
Author: Fenella J. Kirkham ORCID iD

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