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

Autor: Pascal Rihet, Sarwat Afridi, Alexandre Atkinson, Séverine Garnier, Francis Fumoux
Přispěvatelé: Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), BMC, Ed.
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
HS3ST3B1
Parasitemia
medicine.disease_cause
Plasmodium chabaudi
Mice
0302 clinical medicine
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Malaria
Falciparum
Child
Genetics
0303 health sciences
Mutation
Parasitaemia
Genetic interaction
HS3ST3A1
Infectious Diseases
Heparan sulphate biosynthesis
Child
Preschool
Chromosomal region
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Female
Sulfotransferases
Adult
Plasmodium falciparum
lcsh:Arctic medicine. Tropical medicine
Adolescent
lcsh:RC955-962
Single-nucleotide polymorphism
Biology
lcsh:Infectious and parasitic diseases
03 medical and health sciences
Young Adult
Genetic variation
Burkina Faso
parasitic diseases
medicine
Animals
Humans
lcsh:RC109-216
Gene
030304 developmental biology
Family Health
Research
Genetic Variation
biology.organism_classification
medicine.disease
Biosynthetic Pathways
Malaria
Family-based association
Parasitology
Heparitin Sulfate
030217 neurology & neurosurgery
Zdroj: Malaria Journal
Malaria Journal, 2012, 11 (1), pp.108. ⟨10.1186/1475-2875-11-108⟩
Malaria Journal, BioMed Central, 2012, 11 (1), pp.108. ⟨10.1186/1475-2875-11-108⟩
Malaria Journal, Vol 11, Iss 1, p 108 (2012)
ISSN: 1475-2875
Popis: 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.
Databáze: OpenAIRE
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