Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2)

Numerous reports have suggested that immunogenetic factors may influence HIV-1 acquisition, yet replicated findings that translate between study cohorts remain elusive. Our work aimed to test several hypotheses about genetic variants within the IL10-IL24 gene cluster that encodes interleukin (IL)-10...

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Main Authors:	Li, Xuelin, Zhang, Kui, Pajewski, Nicholas M., Brill, Ilene, Prentice, Heather A., Shrestha, Sadeep, Kilembe, William, Karita, Etiene, Allen, Susan, Hunter, Eric, Kaslow, Richard A., Tang, Jianming
Format:	Online
Language:	English
Published:	2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409473/

id	pubmed-4409473
recordtype	oai_dc
spelling	pubmed-44094732015-10-01 Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2) Li, Xuelin Zhang, Kui Pajewski, Nicholas M. Brill, Ilene Prentice, Heather A. Shrestha, Sadeep Kilembe, William Karita, Etiene Allen, Susan Hunter, Eric Kaslow, Richard A. Tang, Jianming Article Numerous reports have suggested that immunogenetic factors may influence HIV-1 acquisition, yet replicated findings that translate between study cohorts remain elusive. Our work aimed to test several hypotheses about genetic variants within the IL10-IL24 gene cluster that encodes interleukin (IL)-10, IL-19, IL-20, and IL-24. In aggregated data from 515 Rwandans and 762 Zambians with up to 12 years of follow-up, 190 single nucleotide polymorphisms (SNPs) passed quality control procedures. When HIV-1-exposed seronegative subjects (n = 486) were compared with newly seroconverted individuals (n = 313) and seroprevalent subjects (n = 478) who were already infected at enrollment, rs12407485 (G>A) in IL19 showed a robust association signal in adjusted logistic regression models (odds ratio = 0.64, P = 1.7 × 10−4, and q = 0.033). Sensitivity analyses demonstrated that (i) results from both cohorts and subgroups within each cohort were highly consistent; (ii) verification of HIV-1 infection status after enrollment was critical; and (iii) supporting evidence was readily obtained from Cox proportional hazards models. Data from public databases indicate that rs12407485 is part of an enhancer element for three transcription factors. Overall, these findings suggest that molecular features at the IL19 locus may modestly alter the establishment of HIV-1 infection. 2015-01-29 2015 /pmc/articles/PMC4409473/ /pubmed/25633979 http://dx.doi.org/10.1038/gene.2014.84 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Li, Xuelin Zhang, Kui Pajewski, Nicholas M. Brill, Ilene Prentice, Heather A. Shrestha, Sadeep Kilembe, William Karita, Etiene Allen, Susan Hunter, Eric Kaslow, Richard A. Tang, Jianming
spellingShingle	Li, Xuelin Zhang, Kui Pajewski, Nicholas M. Brill, Ilene Prentice, Heather A. Shrestha, Sadeep Kilembe, William Karita, Etiene Allen, Susan Hunter, Eric Kaslow, Richard A. Tang, Jianming Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2)
author_facet	Li, Xuelin Zhang, Kui Pajewski, Nicholas M. Brill, Ilene Prentice, Heather A. Shrestha, Sadeep Kilembe, William Karita, Etiene Allen, Susan Hunter, Eric Kaslow, Richard A. Tang, Jianming
author_sort	Li, Xuelin
title	Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2)
title_short	Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2)
title_full	Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2)
title_fullStr	Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2)
title_full_unstemmed	Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2)
title_sort	immunogenetic influences on acquisition of hiv-1 infection: consensus findings from two african cohorts point to an enhancer element in il19 (1q32.2)
description	Numerous reports have suggested that immunogenetic factors may influence HIV-1 acquisition, yet replicated findings that translate between study cohorts remain elusive. Our work aimed to test several hypotheses about genetic variants within the IL10-IL24 gene cluster that encodes interleukin (IL)-10, IL-19, IL-20, and IL-24. In aggregated data from 515 Rwandans and 762 Zambians with up to 12 years of follow-up, 190 single nucleotide polymorphisms (SNPs) passed quality control procedures. When HIV-1-exposed seronegative subjects (n = 486) were compared with newly seroconverted individuals (n = 313) and seroprevalent subjects (n = 478) who were already infected at enrollment, rs12407485 (G>A) in IL19 showed a robust association signal in adjusted logistic regression models (odds ratio = 0.64, P = 1.7 × 10−4, and q = 0.033). Sensitivity analyses demonstrated that (i) results from both cohorts and subgroups within each cohort were highly consistent; (ii) verification of HIV-1 infection status after enrollment was critical; and (iii) supporting evidence was readily obtained from Cox proportional hazards models. Data from public databases indicate that rs12407485 is part of an enhancer element for three transcription factors. Overall, these findings suggest that molecular features at the IL19 locus may modestly alter the establishment of HIV-1 infection.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409473/
_version_	1613215580222914560

Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2)

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