Immunogenetic influences on acquisition of HIV-1 infection: Consensus findings from two African cohorts point to an enhancer element in IL19 ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-01-29

AUTHORS

Xuelin Li, Kui Zhang, Nicholas M. Pajewski, Ilene Brill, Heather A. Prentice, Sadeep Shrestha, William Kilembe, Etiene Karita, Susan Allen, Eric Hunter, Richard A. Kaslow, Jianming Tang

ABSTRACT

Numerous reports have suggested that immunogenetic factors may influence human immunodeficiency virus (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 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. More... »

PAGES

213-220

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/gene.2014.84

DOI

http://dx.doi.org/10.1038/gene.2014.84

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033212636

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25633979


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36 schema:description Numerous reports have suggested that immunogenetic factors may influence human immunodeficiency virus (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 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.
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44 Cox proportional hazards model
45 HIV-1 infection
46 HIV-1 infection status
47 HIV-1-exposed seronegative subjects
48 IL-19
49 IL-20
50 IL-24
51 IL10-IL24 gene cluster
52 IL19
53 IL19 locus
54 Rwandans
55 Zambians
56 acquisition
57 analysis
58 association signals
59 clusters
60 cohort
61 consensus findings
62 control procedures
63 data
64 database
65 elements
66 enhancer elements
67 enrollment
68 establishment
69 evidence
70 factors
71 features
72 findings
73 gene cluster
74 genetic variants
75 hazards model
76 human immunodeficiency virus
77 hypothesis
78 immunodeficiency virus
79 immunogenetic factors
80 immunogenetic influences
81 individuals
82 infection
83 infection status
84 influence
85 interleukin
86 loci
87 logistic regression models
88 model
89 molecular features
90 numerous reports
91 part
92 polymorphism
93 procedure
94 proportional hazards model
95 public databases
96 quality control procedures
97 regression models
98 report
99 robust association signals
100 rs12407485
101 sensitivity analysis
102 seronegative subjects
103 seroprevalent subjects
104 signals
105 single nucleotide polymorphisms
106 status
107 study cohort
108 subgroups
109 subjects
110 transcription factors
111 translates
112 variants
113 verification
114 virus
115 work
116 years
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