Anaemia in pregnant Zanzibari women: do common genetic polymporhisms affecting iron metabolism explain different responses to iron supplementation? (360G-Wellcome-079915_Z_06_Z)

Anaemia in pregnancy threatens maternal and infant health in developing countries. Measures to control anaemia have been less successful than anticipated. Even in carefully controlled interventions there is large variability in response to iron supplementation. In malaria-endemic areas there are strong interactions between host-genetic factors, malaria infection and haematological outcomes. Polymorphisms in the haptoglobin gene determine how iron is recycled following haemolysis. We have evidence from The Gambia that haptoglobin variants affect susceptibility to malaria-induced anaemia more strongly than other previously known genetic variants. This study will test whether haptoglobin gene polymorphisms influence anaemia rates in pregnant Zanzibari women and modulate the effects of iron supplementation on haemoglobin responses. We will analyse haptoglobin, G6PD, alpha- thalassaemia and HbS genotypes in 1303 women previously enrolled in a maternal iron supplementation trial (Mama na Afya Trial) for whom antenatal, anthropometric, haematological and malariometric data are already available. We hypothesise that the Hp2-2 genotype will predispose to greater malaria-induced anaemia and less efficient utilisation of exogenous iron. Putative mechanisms will be explored through cross-sectional analysis of haptoglobin polymorphisms and markers of iron and redox status in third trimester pregnant women (n=254). Understanding factors leading to defective iron recycling could help the development of new intervention strategies.