Evidence of positively selected G6PD A- allele reduces risk of Plasmodium falciparum infection in African population on Bioko Island

Mol Genet Genomic Med. 2020 Feb;8(2):e1061. doi: 10.1002/mgg3.1061. Epub 2019 Dec 24.

Abstract

Background: Glucose-6-phosphate dehydrogenase (G6PD) is an essential enzyme that protects red blood cells from oxidative damage. Although G6PD-deficient alleles appear to confer a protective effect of malaria, the link with clinical protection against Plasmodium infection is conflicting.

Methods: A case-control study was conducted on Bioko Island, Equatorial Guinea and further genotyping analysis used to detect natural selection of the G6PD A- allele.

Results: Our results showed G6PD A- allele could significantly reduce the risk of Plasmodium falciparum infection in male individuals (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.20-0.93; p < .05) and homozygous female individuals (AOR, 0.11; 95% CI, 0.01-0.84; p < .05). Additionally, the parasite densities were significantly different in the individuals with different G6PD A- alleles and individual levels of G6PD enzyme activity. The pattern of linkage disequilibrium and results of the long-range haplotype test revealed a strong selective signature in the region encompassing the G6PD A- allele over the past 6,250 years. The network of inferred haplotypes suggested a single origin of the G6PD A- allele in Africans.

Conclusion: Our findings demonstrate that glucose-6-phosphate dehydrogenase (G6PD) A- allele could reduce the risk of P. falciparum infection in the African population and indicate that malaria has a recent positive selection on G6PD A- allele.

Keywords: EHH; G6PD (A-) deficiency; malaria; natural selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles*
  • Black People / genetics
  • Child
  • Child, Preschool
  • Female
  • Glucosephosphate Dehydrogenase / genetics*
  • Guinea
  • Homozygote
  • Humans
  • Infant
  • Islands
  • Linkage Disequilibrium
  • Malaria / genetics*
  • Male
  • Plasmodium falciparum / pathogenicity
  • Polymorphism, Single Nucleotide
  • Population / genetics*
  • Selection, Genetic*

Substances

  • G6PD protein, human
  • Glucosephosphate Dehydrogenase