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

Malaria Journal

Research

Francis Fumoux¹  Séverine Garnier²  Sarwat Afridi²  Pascal Rihet²  Alexandre Atkinson² 

[1] UMR-MD3, 27 Boulevard Jean Moulin, F-13385, Marseille, France;Aix-Marseille University, F-13288, Marseille, France;UMR928-TAGC, INSERM, 163 Av de Luminy, F-13288, Marseille, France;Aix-Marseille University, F-13288, Marseille, France;

关键词: HS3ST3A1;    HS3ST3B1;    Heparan sulphate biosynthesis;    Plasmodium falciparum;    Malaria;    Parasitaemia;    Family-based association;    Genetic interaction;   

DOI  :  10.1186/1475-2875-11-108

 received in 2012-01-30, accepted in 2012-04-04,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThere 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.MethodsPolymorphisms 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.ResultsLinkage 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.ConclusionGenetic 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.

【 授权许可】

Unknown   
© Atkinson et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.