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) polymorphi...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | Inglés |
| Published: |
Wiley
2014
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10568/52228 |
| _version_ | 1855521282400976896 |
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| author | Cox, S.E. Makani, J. Soka, D. L'Esperance, V.S. Kija, E. Domínguez Salas, Paula Newton, C.R.J. Birch, A.A. Prentice, A.M. Kirkham, F.J. |
| author_browse | Birch, A.A. Cox, S.E. Domínguez Salas, Paula Kija, E. Kirkham, F.J. L'Esperance, V.S. Makani, J. Newton, C.R.J. Prentice, A.M. Soka, D. |
| author_facet | Cox, S.E. Makani, J. Soka, D. L'Esperance, V.S. Kija, E. Domínguez Salas, Paula Newton, C.R.J. Birch, A.A. Prentice, A.M. Kirkham, F.J. |
| author_sort | Cox, S.E. |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | 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. |
| format | Journal Article |
| id | CGSpace52228 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 2014 |
| publishDateRange | 2014 |
| publishDateSort | 2014 |
| publisher | Wiley |
| publisherStr | Wiley |
| record_format | dspace |
| spelling | CGSpace522282023-10-16T14:03:31Z Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania Cox, S.E. Makani, J. Soka, D. L'Esperance, V.S. Kija, E. Domínguez Salas, Paula Newton, C.R.J. Birch, A.A. Prentice, A.M. Kirkham, F.J. pathology health 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. 2014-06 2014-12-17T07:03:59Z 2014-12-17T07:03:59Z Journal Article https://hdl.handle.net/10568/52228 en Open Access Wiley Cox, S.E., Makani, J., Soka, D., L'Esperance, V.S., Kija, E., Dominguez-Salas, P., Newton, C.R.J., Birch, A.A., Prentice, A.M. and Kirkham, F.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. |
| spellingShingle | pathology health Cox, S.E. Makani, J. Soka, D. L'Esperance, V.S. Kija, E. Domínguez Salas, Paula Newton, C.R.J. Birch, A.A. Prentice, A.M. Kirkham, F.J. Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania |
| title | Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania |
| title_full | Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania |
| title_fullStr | Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania |
| title_full_unstemmed | Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania |
| title_short | Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania |
| title_sort | haptoglobin alpha thalassaemia and glucose 6 phosphate dehydrogenase polymorphisms and risk of abnormal transcranial doppler among patients with sickle cell anaemia in tanzania |
| topic | pathology health |
| url | https://hdl.handle.net/10568/52228 |
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