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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Host genetics and immune control of HIV-1 infection: Fine mapping for the extended human MHC region in an African cohort
Genes and Immunity, Volume 15, No. 5, Year 2014
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Description
Multiple major histocompatibility complex (MHC) loci encoding human leukocyte antigens (HLA) have allelic variants unequivocally associated with differential immune control of HIV-1 infection. Fine mapping based on single nucleotide polymorphisms (SNPs) in the extended MHC (xMHC) region is expected to reveal causal or novel factors and to justify a search for functional mechanisms. We have tested the utility of a custom fine-mapping platform (the ImmunoChip) for 172 HIV-1 seroconverters (SCs) and 449 seroprevalent individuals (SPs) from Lusaka, Zambia, with a focus on more than 6400 informative xMHC SNPs. When conditioned on HLA and nongenetic factors previously associated with HIV-1 viral load (VL) in the study cohort, penalized approaches (HyperLasso models) identified an intergenic SNP (rs3094626 between RPP21 and HLA-E) and an intronic SNP (rs3134931 in NOTCH4) as novel correlates of early set-point VL in SCs. The minor allele of rs2857114 (downstream from HLA-DOB) was an unfavorable factor in SPs. Joint models based on demographic features, HLA alleles and the newly identified SNP variants could explain 29% and 15% of VL variance in SCs and SPs, respectively. These findings and bioinformatics strongly suggest that both classic and nonclassic MHC genes deserve further investigation, especially in Africans with relatively short haplotype blocks. © 2014 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
Prentice, Heather A.
United States, Birmingham
The University of Alabama at Birmingham
United States, Silver Spring
Military Hiv Research Program
Pajewski, Nicholas M.
United States, Winston Salem
Wake Forest University School of Medicine
He, Dongning
United States, Birmingham
The University of Alabama at Birmingham
Zhang, Kui
United States, Birmingham
The University of Alabama at Birmingham
Brown, E. E.
United States, Birmingham
The University of Alabama at Birmingham
Kilembe, William
Zambia, Lusaka
Zambia-emory Hiv Research Project
Allen, Susan A.
Zambia, Lusaka
Zambia-emory Hiv Research Project
United States, Atlanta
Emory University
Hunter, Eric
United States, Atlanta
Emory University
Kaslow, Richard A.
United States, Birmingham
The University of Alabama at Birmingham
United States, Washington, D.c.
U.s. Department of Veterans Affairs
Tang, Jianming
United States, Birmingham
The University of Alabama at Birmingham
Statistics
Citations: 11
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1038/gene.2014.16
ISSN:
14664879
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study
Study Locations
Zambia