Females of HbAS genotype have reduced concentration of the malaria protective deoxyhemoglobin S than males.

Abstract

The quantity of the intra-erythrocytic deoxyhemoglobin S (Hb S) affects the level of protection against malaria and also the sickling phenomenon. This study reports on significantly lower concentration of Hb S in females than males. Data came from 350 children, aged 12-47 months who participated in a phase 2b malaria vaccine trial. Hemoglobinopathy and G6PD deficiency typing was necessary to ascertain equal representation of these malaria protective traits across the vaccine cohorts. Hemoglobin types (HbAA, HbAS) and % Hb S were evaluated by HPLC. Alpha thalassemia (alpha-thal) and G6PD genotypes were evaluated by PCR. The overall prevalence for HbAS was 20%, 46% for 3 alpha genes and 10% for 2 alpha genes and 14% for G6PD A-. More females of HbAS/αα/αα genotype had low Hb S than males and had mean % Hb S of 37.5% ± 5.4 SD, compared to 42.0% ± 2.5 SD in males of same genotype (P = 0.018). Consistent with reduction of the malaria protective Hb S in females, parasite load in females was nearly twice that of males but the difference was not statistically significant. The X-chromosome linked G6PD deficiency did not influence the level of Hb S. We conclude that, the low Hb S in these females explains the resultant higher malaria parasite load. We speculate that the low Hb S in females could also explain observations suggesting that the sickling phenomenon tends to be less severe in females than males.

• Authors: John N Waitumbi, Carolyne M Kifude, Carol W Hunja, Bernhards R Ogutu
• Journal: PloS one (PLoS One) Vol. 13 Issue 9 Pg. e0203455 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 30204801 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Hemoglobin, Sickle
• Hemoglobins
• Malaria Vaccines
• deoxyhemoglobin

Topics

• Child, Preschool
• Female
• Genotype
• Glucosephosphate Dehydrogenase Deficiency (blood, genetics)
• Hemoglobin, Sickle (genetics, metabolism)
• Hemoglobins (genetics, metabolism)
• Humans
• Infant
• Malaria (blood, prevention & control)
• Malaria Vaccines (administration & dosage)
• Male
• Sex Characteristics
• alpha-Thalassemia (blood, genetics)