Scientific Publications
- PMID: 24784026
- Title: Host genetics and immune control of HIV 1 infection fine mapping for the extended human MHC region in an African cohort
- Abstract: 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.
- Date: 1970-08-22
- Year: 2015
- Journal: Genes Immun.
- PMID Author: Prentice HA, Pajewski NM, He D, Zhang K, Brown EE, Kilembe W, Allen S, Hunter E, Kaslow RA, Tang J
- PMC Link #: PMC4111776
Host genetics and immune control of HIV 1 infection fine mapping for the extended human MHC region in an African cohort
Host genetics and immune control of HIV-1 infection: fine mapping for the extended human MHC region in an African cohort. Genes Immun. ;15(5):275-81 doi: 10.1038/gene.2014.16
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