Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria
Human Molecular Genetics, Volume 17, No. 4, Year 2008
Notification
URL copied to clipboard!
Description
There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common ABO alleles means that even modest differences in susceptibility could have a significant impact on the health of people living in malaria endemic regions. We performed an association study, the first to utilize key molecular genetic variation underlying the ABO system, genotyping >9000 individuals across three African populations. Using population- and family-based tests, we demonstrated that alleles producing functional ABO enzymes are associated with greater risk of severe malaria phenotypes (particularly malarial anemia) in comparison with the frameshift deletion underlying blood group O: case-control allelic odds ratio (OR), 1.2; 95% confidence interval (CI), 1.09-1.32; P = 0.0003; family-studies allelic OR, 1.19; 95% CI, 1.08-1.32; P = 0.001; pooled across all studies allelic OR, 1.18; 95% CI, 1.11-1.26; P = 2 × 10-7. We found suggestive evidence of a parent-of-origin effect at the ABO locus by analyzing the family trios. Non-O haplotypes inherited from mothers, but not fathers, are significantly associated with severe malaria (likelihood ratio test of Weinberg, P = 0.046). Finally, we used HapMap data to demonstrate a region of low FST (-0.001) between the three main HapMap population groups across the ABO locus, an outlier in the empirical distribution of FST across chromosome 9 (∼99.5-99.9th centile). This low FST region may be a signal of long-standing balancing selection at the ABO locus, caused by multiple infectious pathogens including P. falciparum. © The Author 2007. Published by Oxford University Press. All rights reserved.
Authors & Co-Authors
Fry, Andrew E.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Griffiths, Michael John
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Kenya, Nairobi
Kenya Medical Research Institute
Auburn, Sarah A.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Diakité, Mahamadou L.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Forton, Julian T.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Green, Angie L.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Richardson, Anna
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Wilson, Jonathan N.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Jallow, Muminatou
Gambia, Banjul
Medical Research Council Laboratories Gambia
Sisay-Joof, Fatoumatta
Gambia, Banjul
Medical Research Council Laboratories Gambia
Pinder, Margaret
Gambia, Banjul
Medical Research Council Laboratories Gambia
Peshu, Norbert M.
Kenya, Nairobi
Kenya Medical Research Institute
Williams, Thomas Neil
Kenya, Nairobi
Kenya Medical Research Institute
United Kingdom, Oxford
John Radcliffe Hospital
Marsh, Kevin
Kenya, Nairobi
Kenya Medical Research Institute
United Kingdom, Oxford
John Radcliffe Hospital
Molyneux, Malcolm Edward
Malawi, Blantyre
Malawi-liverpool-wellcome Trust Clinical Research Programme
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Taylor, Terrie Ellen
Malawi, Zomba
University of Malawi
United States, East Lansing
Msu College of Osteopathic Medicine
Rockett, Kirk A.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Kwiatkowski, Dominic P.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, Hinxton
Wellcome Sanger Institute
Statistics
Citations: 192
Authors: 18
Affiliations: 9
Identifiers
Doi:
10.1093/hmg/ddm331
ISSN:
09646906
e-ISSN:
14602083
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Case-Control Study