title: Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania.
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.
authors.affiliation: MRC International Nutrition Group, London School of Hygiene & Tropical Medicine, London, UK; Muhimbili Wellcome Programme, Muhimbili University of Health & Allied Sciences, Dar es Salaam, Tanzania.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Cox
authors.forename: Julie
authors.initials: J
authors.lastname: Makani
authors.forename: Deogratias
authors.initials: D
authors.lastname: Soka
authors.forename: Veline S
authors.initials: VS
authors.lastname: L'Esperence
authors.forename: Edward
authors.initials: E
authors.lastname: Kija
authors.forename: Paula
authors.initials: P
authors.lastname: Dominguez-Salas
authors.forename: Charles R J
authors.initials: CR
authors.lastname: Newton
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Birch
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.forename: Fenella J
authors.initials: FJ
authors.lastname: Kirkham
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000235:genetics / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000235:genetics / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D004843:Epistasis, Genetic; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D006242:Haptoglobins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods; D055815:Young Adult; D017085:alpha-Thalassemia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology
chemical_list: D006242:Haptoglobins; D005954:Glucosephosphate Dehydrogenase
keywords: Africa; cerebral blood flow velocity; children; sickle cell disease