A haptoglobin gene promoter polymorphism (A‐61C) protects from anaemia in pregnant Zanzibari women

Abstract

This study aims to determine whether polymorphisms in the haptoglobin (Hp) gene (a haemoglobin (Hb)-chelating acute phase protein) influence susceptibility to anaemia and malaria in pregnant Zanzibari women. We analysed haptoglobin, G6PD, and sickle haemoglobin (HbS) genotypes in 1221 women enrolled in a multivitamin supplementation trial with antenatal, anthropometric, haematological and malariometric data. After adjusting for age, gestational age, urban/rural, prior use of antimalarials and multivitamins, and trial arm, the A-61C mutant allele (prevalence=14.1%) in the promoter region of the Hp gene was found to protect from anaemia at presentation to antenatal clinic (OR=0.65; [95%CI 0.45–0.93] p=0.04) and at week 32 of gestation (OR=0.67; [95%CI 0.48–0.93] p=0.03). There was no effect on anaemia at week 36 of gestation (possibly due to smaller sample size and lower prevalence of anaemia) however at week 36, women with the A-61C mutation had a 3.5g/L advantage in mean Hb compared to those with wildtype (p=0.03). No women were homozygote for HbS. No genotypes were associated with susceptibility to malaria including HbAS, even in primigravidae. We have elsewhere reported the A-61C mutation to be protective for malaria in children. This effect was not seen in pregnant women, possibly as a result of acquired immunity with age. However it does appear to have a protective effect on anaemia throughout pregnancy.