Haptoglobin genotype, anaemia and malaria in Gambian children.
OBJECTIVE
To retest our previous finding that the haptoglobin (Hp) 22 genotype is associated with seasonal anaemia, and to investigate the role of malaria in this effect.


METHODS
Haemoglobin (Hb) and peripheral parasitaemia were assessed at pre- and post-malarial season cross-sectional surveys in rural Gambian children aged 10-72 months. Between the surveys, active longitudinal surveillance was conducted to detect febrile episodes.


RESULTS
Unlike previously, no overall reduction in Hb was observed (Hb = 106.1 vs. 107.2 g/l, P = 0.13, n = 545). However, multi-variable linear regression revealed differences in Hb over the season by Hp and Hb-sickle (HbS) genotype (-2.20 g/l per copy of the Hp2 allele, P = 0.043; HbAS vs. HbAA + 3.13 g/l, P = 0.11, n = 536). There was no effect of malarial episodes during follow-up; this suggests that when effective treatment is given, Hb levels recover. The A61-C Hp promoter SNP, associated with the Hp2 allele, had no effect.


CONCLUSIONS
The effect of the Hp2 allele appears to be independent of effects on malaria incidence but may affect Hb levels through increased oxidant stress and red cell turnover. This may be supported by our previous observations that the effect of Hp22 was independent of markers of iron status and zinc protoporphyrin measured at the cross-sectional surveys and therefore also of iron availability for erythropoiesis.
Cox
Sharon E
SE
MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, UK. sharon.cox@lshtm.ac.uk
Doherty
Conor P
CP
Atkinson
Sarah H
SH
Nweneka
Chidi V
CV
Fulford
Anthony J C
AJ
Sirugo
Giorgio
G
Rockett
Kirk A
KA
Kwiatkowski
Dominic P
DP
Prentice
Andrew M
AM
D000740:Anemia / Q000453:epidemiology / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005714:Gambia / Q000453:epidemiology; D005838:Genotype; D006242:Haptoglobins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007223:Infant; D008288:Malaria / Q000453:epidemiology / Q000235:genetics; D008297:Male; D015999:Multivariate Analysis; D018512:Parasitemia / Q000453:epidemiology / Q000235:genetics; D015995:Prevalence; D012621:Seasons
D015415:Biomarkers; C485359:HP protein, human; D006242:Haptoglobins