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J Infect Dis. 2015 Oct 1;212(7):1129-39. doi: 10.1093/infdis/jiv192. Epub 2015 Mar 24.

USP38, FREM3, SDC1, DDC, and LOC727982 Gene Polymorphisms and Differential Susceptibility to Severe Malaria in Tanzania.

Author information

  • 1Joint Malaria Programme, Kilimanjaro Christian Medical College, Moshi National Institute for Medical Research, Dar es Salaam, Tanzania.
  • 2Departments of Immunology and Infection Centre of Statistics and Applications, University of Lisbon, Portugal.
  • 3Clinical Research.
  • 4Joint Malaria Programme, Kilimanjaro Christian Medical College, Moshi.
  • 5Joint Malaria Programme, Kilimanjaro Christian Medical College, Moshi Departments of Immunology and Infection.
  • 6Pathogen Molecular Biology Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom.


Populations exposed to Plasmodium falciparum infection develop genetic mechanisms of protection against severe malarial disease. Despite decades of genetic epidemiological research, the sickle cell trait (HbAS) sickle cell polymorphism, ABO blood group, and other hemoglobinopathies remain the few major determinants in severe malaria to be replicated across different African populations and study designs. Within a case-control study in a region of high transmission in Tanzania (n = 983), we investigated the role of 40 new loci identified in recent genome-wide studies. In 32 loci passing quality control procedures, we found polymorphisms in USP38, FREM3, SDC1, DDC, and LOC727982 genes to be putatively associated with differential susceptibility to severe malaria. Established candidates explained 7.4% of variation in severe malaria risk (HbAS polymorphism, 6.3%; α-thalassemia, 0.3%; ABO group, 0.3%; and glucose-6-phosphate dehydrogenase deficiency, 0.5%) and the new polymorphisms, another 4.3%. The regions encompassing the loci identified are promising targets for the design of future treatment and control interventions.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.


Plasmodium falciparum; Tanzania; genetic association study; host susceptibility; severe malaria

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