USP38, FREM3, SDC1, DDC and LOC727982 gene polymorphisms and differential susceptibility to severe malaria in Tanzania.


Manjurano, A; Sepúlveda, N; Nadjm, B; Mtove, G; Wangai, H; Maxwell, C; Olomi, R; Reyburn, H; Drakeley, CJ; Riley, EM; Clark, TG; in Collaboration With MalariaGEN, ; (2015) USP38, FREM3, SDC1, DDC and LOC727982 gene polymorphisms and differential susceptibility to severe malaria in Tanzania. The Journal of infectious diseases, 212 (7). pp. 1129-39. ISSN 0022-1899 DOI: 10.1093/infdis/jiv192

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Abstract

: 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.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Malaria Centre
PubMed ID: 25805752
Web of Science ID: 363191300014
URI: http://researchonline.lshtm.ac.uk/id/eprint/2137769

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