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. 2012 Apr 4:11:108.
doi: 10.1186/1475-2875-11-108.

Genetic variations in genes involved in heparan sulphate biosynthesis are associated with Plasmodium falciparum parasitaemia: a familial study in Burkina Faso

Alexandre Atkinson  1 , Séverine Garnier, Sarwat Afridi, Francis Fumoux, Pascal Rihet
Affiliations

Genetic variations in genes involved in heparan sulphate biosynthesis are associated with Plasmodium falciparum parasitaemia: a familial study in Burkina Faso

Alexandre Atkinson et al. Malar J. .

Abstract

Background: There is accumulating evidence that host heparan sulphate proteoglycans play an important role in the life cycle of Plasmodium through their heparan sulphate chains, suggesting that genetic variations in genes involved in heparan sulphate biosynthesis may influence parasitaemia. Interestingly, Hs3st3a1 and Hs3st3b1 encoding enzymes involved in the biosynthesis of heparan sulphate are located within a chromosomal region linked to Plasmodium chabaudi parasitaemia in mice. This suggests that HS3ST3A1 and HS3ST3B1 may influence P. falciparum parasitaemia in humans.

Methods: Polymorphisms within HS3ST3A1 and HS3ST3B1 were identified in 270 individuals belonging to 44 pedigrees and living in Burkina Faso. Linkage and association between parasitaemia and the polymorphisms were assessed with MERLIN and FBAT. A genetic interaction analysis was also conducted based on the PGMDR approach.

Results: Linkage between P. falciparum parasitaemia and the chromosomal region containing HS3ST3A1 and HS3ST3B1 was detected on the basis of the 20 SNPs identified. In addition, rs28470223 located within the promoter of HS3ST3A1 was associated with P. falciparum parasitaemia, whereas the PGMDR analysis revealed a genetic interaction between HS3ST3A1 and HS3ST3B1. Seventy-three significant multi-locus models were identified after correcting for multiple tests; 37 significant multi-locus models included rs28470223, whereas 38 multi-locus models contained at least one mis-sense mutation within HS3ST3B1.

Conclusion: Genetic variants of HS3ST3A1 and HS3ST3B1 are associated with P. falciparum parasitaemia. This suggests that those variants alter both the function of heparan sulphate proteoglycans and P. falciparum parasitaemia.

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Figures

Figure 1
Figure 1
(A) Diagram of the HS3ST3A1/HS3ST3B1 locus. (B) Location of the known SNPs in relation to the intron/exon structure of HS3ST3A1 and HS3ST3B1. The SNPs that were detected are in bold. The 5'- and 3'-UTRs are shown by white boxes and the coding exons are shown by hatched boxes. The regions that encode the sulphotransferase domain are shown.
Figure 2
Figure 2
Pair-wise linkage disequilibrium map within HS3ST3A1 and HS3ST3B1. Dark denotes highly significant linkage disequilibrium. R2 multiplied by 100 value is shown.
See this image and copyright information in PMC

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