Transferrin Polymorphisms in Childhood Malarial Anaemia in the Gabonese Children

Severe malarial anaemia (SMA) is one of the most outstanding complications of malaria in African children. It is often associated with iron deficiency, but explorations of soluble transferrin revealed controversial data. Despite the implication of host genetics factors in malaria pathogenesis, nothing is known about the role of iron carried polymorphisms in this plague. Nevertheless, these polymorphisms have been associated with pathogenesis of diseases associated with iron deficiency.We conducted a cross-sectional study including 59 children with SMA, 176 with mild malaria anaemia (MMA) and 92 with non-anaemia malaria (NAM). We investigated polymorphisms G258S, R300H, A477P, P570S from transferrin exons 7, 8, 12, 15 respectively and S142G from transferrin receptor1 (TfR1) exon 4 by PCR-RFLP. The mean age of children with SMA, MMA and NAM was 27.7 ± 8.8, 38.6 ± 10.2 and 47.3± 15.4 months respectively, confirming that SMA is associated with young age (pI0.05). Alleles of transferrin C2 (corresponding to P570S) and C3 (corresponding to G258S) occurred in 13.8% and 1.2% of the children, respectively. Allele C3 was detected only in children with SMA (n=4, 6.8%). The frequency of allele C2 was significantly different between study groups: 1.7%, 11.4%, and 26.2% respectively for SMA, MMA, NAM; pI0.0003. Allele of transferrin C2 was associated with decreased risk in malarial anaemia (malarial anaemia [8.9%] versus NAM [26.2%], pI0.01). Transferrin polymorphisms R300H and A477P were not found. The frequency of TfR1 polymorphism S142G was 13.6%, 12.5%, 13.0% respectively for SMA, MMA, and NAM, suggesting that it had no influence on the risk of malarial anaemia. Data support the conclusion that transferrin polymorphisms influence the risk of SMA.