The online version of this article (doi:10.1186/1475-2875-11-108) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
AA carried out the molecular genetic studies, participated in the sequence alignment and performed the statistical analysis. SG participated in the molecular genetic studies and sequence alignment. SA participated in the statistical analysis. FF participated in the design of the study, and revised the results and the manuscript. PR performed the design of the study, supervised the experiments and the statistical analyses, and wrote the manuscript. All authors read and approved the final manuscript.
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.
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.
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.
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.
Additional file 1: Primer pairs and annealing temperatures used to amplify HS3ST3A1 and HS3ST3B1. (DOC 32 KB)12936_2012_2089_MOESM1_ESM.DOC
Additional file 2: The best multi-locus models identified with PGMDR. All the P values were significant after applying a FDR of 5%. (XLS 38 KB)12936_2012_2089_MOESM2_ESM.XLS
Authors’ original file for figure 112936_2012_2089_MOESM3_ESM.png
Authors’ original file for figure 212936_2012_2089_MOESM4_ESM.png
Coppi A, Tewari R, Bishop JR, Bennett BL, Lawrence R, Esko JD, Billker O, Sinnis P: Heparan sulphate proteoglycans provide a signal to Plasmodium sporozoites to stop migrating and productively invade host cells. Cell Host Microbe. 2007, 2: 316-327. 10.1016/j.chom.2007.10.002. PubMedCentralCrossRefPubMed
Chen Q, Barragan A, Fernandez V, Sundstrom A, Schlichtherle M, Sahlen A, Carlson J, Datta S, Wahlgren M: Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum. J Exp Med. 1998, 187: 15-23. 10.1084/jem.187.1.15. PubMedCentralCrossRefPubMed
Prydz K, Dalen KT: Synthesis and sorting of proteoglycans. J Cell Sci. 2000, 113 (Pt 2): 193-205. PubMed
Shworak NW, Liu J, Petros LM, Zhang L, Kobayashi M, Copeland NG, Jenkins NA, Rosenberg RD: Multiple isoforms of heparan sulphate D-glucosaminyl 3-O-sulfotransferase. Isolation, characterization, and expression of human cdnas and identification of distinct genomic loci. J Biol Chem. 1999, 274: 5170-5184. 10.1074/jbc.274.8.5170. CrossRefPubMed
Sakuntabhai A, Ndiaye R, Casademont I, Peerapittayamongkol C, Rogier C, Tortevoye P, Tall A, Paul R, Turbpaiboon C, Phimpraphi W, Trape JF, Spiegel A, Heath S, Mercereau-Puijalon O, Dieye A, Julier C: Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal. PLoS One. 2008, 3: e2000-10.1371/journal.pone.0002000. PubMedCentralCrossRefPubMed
Timmann C, Evans JA, Konig IR, Kleensang A, Ruschendorf F, Lenzen J, Sievertsen J, Becker C, Enuameh Y, Kwakye KO, Opoku E, Browne EN, Ziegler A, Nurnberg P, Horstmann RD: Genome-wide linkage analysis of malaria infection intensity and mild disease. PLoS Genet. 2007, 3: e48-10.1371/journal.pgen.0030048. PubMedCentralCrossRefPubMed
Rozen S, Skaletsky H: Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol. 2000, 132: 365-386. PubMed
Jallow M, Teo YY, Small KS, Rockett KA, Deloukas P, Clark TG, Kivinen K, Bojang KA, Conway DJ, Pinder M, Sirugo G, Sisay-Joof F, Usen S, Auburn S, Bumpstead SJ, Campino S, Coffey A, Dunham A, Fry AE, Green A, Gwilliam R, Hunt SE, Inouye M, Jeffreys AE, Mendy A, Palotie A, Potter S, Ragoussis J, Rogers J, Rowlands K, Somaskantharajah E, Whittaker P, Widden C, Donnelly P, Howie B, Marchini J, Morris A, SanJoaquin M, Achidi EA, Agbenyega T, Allen A, Amodu O, Corran P, Djimde A, Dolo A, Doumbo OK, Drakeley C, Dunstan S, Evans J, Farrar J, Fernando D, Hien TT, Horstmann RD, Ibrahim M, Karunaweera N, Kokwaro G, Koram KA, Lemnge M, Makani J, Marsh K, Michon P, Modiano D, Molyneux ME, Mueller I, Parker M, Peshu N, Plowe CV, Puijalon O, Reeder J, Reyburn H, Riley EM, Sakuntabhai A, Singhasivanon P, Sirima S, Tall A, Taylor TE, Thera M, Troye-Blomberg M, Williams TN, Wilson M, Kwiatkowski DP: Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat Genet. 2009, 41: 657-665. 10.1038/ng.388. PubMedCentralCrossRefPubMed
Moon AF, Edavettal SC, Krahn JM, Munoz EM, Negishi M, Linhardt RJ, Liu J, Pedersen LC: Structural analysis of the sulfotransferase (3-o-sulfotransferase isoform 3) involved in the biosynthesis of an entry receptor for herpes simplex virus 1. J Biol Chem. 2004, 279: 45185-45193. 10.1074/jbc.M405013200. PubMedCentralCrossRefPubMed
Kulane A, Ekre HP, Perlmann P, Rombo L, Wahlgren M, Wahlin B: Effect of different fractions of heparin on Plasmodium falciparum merozoite invasion of red blood cells in vitro. AmJTrop Med Hyg. 1992, 46: 589-594.
- Genetic variations in genes involved in heparan sulphate biosynthesis are associated with Plasmodium falciparum parasitaemia: a familial study in Burkina Faso
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