Genetic Study Indicates two Novel Resistance Loci for Severe Malaria in Africa

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With malaria causing around one million fatalities per year among African children, it is important to understand how the disease is influenced by the environment, anti-malarial drugs and human genetics. However, the full impact of human genetics on resistance to the disease remains largely unexplored.

Professor Andreas Ziegler from the University of Lübeck, Germany, who is taking a 6-month sabbatical at UKZN, presented a lecture at UKZN’s Westville campus on his recent publication in Nature that has identified two novel resistance loci at Human Genome that protects for severe Malaria in Africa.

Professor Ziegler started his lecture by explaining that researchers cannot study malaria in a location where the conditions are not suitable for the parasite to thrive, which is why many researchers of malaria study the infection in Africa, East Asia and South America.  

Professor Ziegler and collaborators examined 2 662 malaria cases and 2 200 controls in Kumasi, Ghana, in order to detect if there is genetic differences that predispose to the disease. The researchers conducted a genome-wide association study (GWAS), an approach which has been used to identify genetic risk factors in many areas, such as cardiology, gastroenterology or oncology. However, in malaria and other infectious diseases, these studies have been only partly successful.

Professor Ziegler explained that malaria genetics are challenging due to the three components: the human being, the environment and the parasite. ‘Malaria infection depends on the age of the patient and their location of the disease, geographically. There are high exposition levels for those of younger age. Gender wise, girls who work in households and have to fetch water have a different exposure to infectious diseases than boys.

‘While age plays a role, there are big variabilities. The researchers took careful control to make sure that the cases and controls matched were in ethnicity, age and gender in order to determine if there were any patterns in the contraction of the disease.’

Through the use of GWAS approach his research group helped to unravel relevant genetic variants that protect against malaria. Professor Ziegler and his colleagues identified two previously unknown loci for severe falciparum malaria. ‘One of the loci was identified on chromosome 1q32 within the ATP2B4 gene, which encodes the main calcium pump of erythrocytes. The second was indicated by an intergenic single nucleotide polymorphism on chromosome 16q22.2, possibly linked to a neighbouring gene encoding the tight-junction protein MARVELD3. The findings underline the potential of the GWAS approach to provide candidates for the development of control measures against infectious diseases in humans.’

 

Publication details: Timmann C, Thye T, Vens M, Evans J, May J, Ehmen C, Sievertsen J, Muntau B, Ruge G, Loag W, Ansong D, Antwi S, Asafo-Adjei E, Nguah SB, Kwakye KO, Akoto AO, Sylverken J, Brendel M, Schuldt K, Loley C, Franke A, Meyer CG, Agbenyega T, Ziegler A, Horstmann RD 2012. Genome-wide association study indicates two novel resistance loci for severe malaria. Nature 489:443-6. doi: 10.1038/nature11334.

 

Professor Andreas Ziegler is Head of the Institute of Medical Biometry and Statistics at Lübeck University, Germany. He is currently a visiting Professor of Biostatistics on sabbatical based in the School of Mathematics, Statistics and Computer Science, Pietermaritzburg campus.

 

The lecture was arranged in association with The Wellcome Trust Africa Centre Genomics Programme, UKZN MRC Flagship project and UKZN’s School of Mathematics, Statistics and Computer Science as part of a monthly seminar series to present multidisciplinary and high-impact research in Africa. For more info on the seminar series, please visit http://www.bioafrica.net/seminars.php

 

Zakia Jeewa