Host Genetic Factors Predisposing to HIV-Associated Neurocognitive Disorder

Kallianpur, Asha R.; Levine, Andrew J.

doi:10.1007/s11904-014-0222-z

Cited by 41 publications

(43 citation statements)

References 144 publications

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“…Despite its potential role in HAND, there are no published studies of DNAm in this context. Indeed, there are very few studies overall on epigenetics and HAND(Desplats et al, 2013; Kazantsev & Thompson, 2008; Mukerjee et al, 2011; Narasipura, Kim, & Al-Harthi, 2014; Saiyed et al, 2011; Sun, Spencer, Chen, Li, & Davie, 2003; Tatro et al, 2010), as recently reviewed (Kallianpur & Levine, 2014; Levine et al, 2014). To our knowledge there have been no peer-reviewed studies examining global (i.e., genome-wide) DNAm in the context of HAND (Perez-Santiago J, 2012).…”

Section: Discussionmentioning

confidence: 99%

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Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders

Levine¹,

et al. 2015

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Objective HIV infection leads to age-related conditions in relatively young persons. HIV-associated neurocognitive disorders (HAND) are considered among the most prevalent of these conditions. To study the mechanisms underlying this disorder, researchers need an accurate method for measuring biological aging. Here we apply a recently developed measure of biological aging, based on DNA methylation, to the study of biological aging in HIV+ brains. Design Retrospective analysis of tissue bank specimens and pre-mortem data. Methods 58 HIV+ adults underwent medical and neurocognitive evaluation within one year of death. DNA was obtained from occipital cortex and analyzed with the Illumina Infinium Human Methylation 450K platform. Biological age determined via the Epigenetic Clock was contrasted with chronological age to obtain a measure of age acceleration, which was then compared between those with HAND and neurocognitively normal individuals. Results The HAND and neurocognitively normal groups did not differ with regard to demographic, histologic, neuropathologic, or virologic variables. HAND was associated with accelerated aging relative to neurocognitively normal individuals, with average relative acceleration of 3.5 years. Age acceleration did not correlate with pre-mortem neurocognitive functioning or HAND severity. Conclusions This is the first study to demonstrate that the epigenetic age of occipital cortex samples is associated with HAND status in HIV+ individuals pre-mortem. While these results suggest that the increased risk of a neurocognitive disorder due to HIV might be mediated by an epigenetic aging mechanism, future studies will be needed to validate the findings and dissect causal relationships and downstream effects.

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Section: Discussionmentioning

confidence: 99%

“…We calculated the CPE, a score that is based on the pharmacokinetic and pharmacodynamic characteristics of antiretroviral medications (Letendre, 2011). CPE scores for the regimen reported at the time of neurocognitive testing were calculated.…”

Section: Methodsmentioning

confidence: 99%

Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders

Levine¹,

et al. 2015

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“…In vitro studies have identified the neurotoxic effects of viral proteins, inflammatory and metabolic agents; however, critical factors contributing to neuropathogenesis in vivo are not completely understood. Polymorphism in TNF-α gene that results in increased secretion in response to bacterial lipopolysaccharide has been observed with increased frequency in HIV-1 seropositive individuals with dementia [16], whereas, mutation in CCL2 (at position 2578G), CCR5Δ32 and other host factors have been identified as neuroprotective[1, 17–19]. While recent work has studied the expression of microRNAs (miRNA) in HAND response [20–24] relatively little is known about their regulatory role and their targets.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analyses identify key cellular factors associated with HIV-1-associated neuropathogenesis in infected men

Venkatachari

Jain

Walker

et al. 2017

Aids

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Objective HIV-1 viral proteins and host inflammatory factors have a direct role in neuronal toxicity in in vitro, however, the contribution of these factors in vivo in HIV-1 associated neurocognitive disorder (HAND) is not fully understood. We applied novel Systems Biology approaches to identify specific cellular and viral factors and their related pathways that are associated with different stages of HAND. Design A cross-sectional study of individuals enrolled in the Multicenter AIDS Cohort Study (MACS) including HIV-1 seronegative (N=36) and HIV-1 seropositive individuals without neurocognitive symptoms (N=16), or with mild neurocognitive disorder (MND) (N=8) or HIV-associated dementia (HAD) (N=16). Methods A systematic evaluation of global transcriptome of peripheral blood mononuclear cells (PBMCs) obtained from HIV-1 seronegative individuals and from HIV-1 positive men without neurocognitive symptoms, or MND or HAD was performed. Results MND and HAD were associated with specific changes in mRNA transcripts and miRNAs in PBMCs. Comparison of upstream regulators and TimePath analyses identified specific cellular factors associated with MND and HAD, while HIV-1 viral proteins played a greater role in HAD. Additionally, expression of specific microRNAs – miR-let-7a, miR-124, miR-15a and others were found to correlate with mRNA gene expression and may have a potential protective role in asymptomatic HIV-1 seropositive individuals by regulating cellular signal transduction pathways downstream of chemokines and cytokines. Conclusions These results identify signature transcriptome changes in PBMCs associated with stages of HAND and shed light on the potential contribution of host cellular factors and viral proteins in HAND development.

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“…It has been suggested that host genetic polymorphisms influence the risk of developing numerous diseases in HIV-infected people. [16][17][18] Estrogene hormone is well known to play an essential role in the growth and development during childhood and estrogen receptors (ERs) mediate much estrogen action.…”

Section: Discussionmentioning

confidence: 99%

Hubungan Polimorfisme Gen Reseptor Estrogen Alfa Dengan Jumlah Sel T Cd4+ Pada Anak Terinfeksi Hiv

Sufiawati¹,

Saptarini²,

Riyanti³

2017

ODONTO : Dental Journal

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Background: Estrogen plays a key role in human physiological processes. Polymorphisms of estrogen receptors have been implicated in the development of numerous diseases. The aim of this study was to evaluate the frequency of ERα gene Pvull and Xbal polymorphisms and assessing their association with CD4+ T-cell counts in HIV-infected children on highly active antiretroviral therapy. Methods: CD4+ T cell counts were determined using the FACS count system. ERα PvuII and XbaI polymorphisms were analyzed by PCR-RFLP. Results: This study enrolled 34 HIV-infected children on HAART. The frequencies of the PvuII and XbaI gene polymorphisms were PP 41,2%, Pp 26,5%, pp 32,4% and XX 35,3%, Xx 17,6%, xx 47,1% respectively. CD4+ T-cell counts were significantly associated with XbaI polymorphisms (p<0.05), but not PvuII polymorphisms (p>0.01). Discussion: Host genetic factor polymorphism is an important determinant of HIV disease progression and treatment response. The ERα Pvull and Xbal polymorphisms can increase risk for the development of HIV-related complication, including oral diseases. Conclusion: The ERα gene XbaI polymorphism was significantly associated with CD4+ T-cell counts. It may explain the role of estrogen in the regulation of HIV replication. Studying human genetic variation in HIV-infected individuals is important to guide a new therapeutic approach.

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Host Genetic Factors Predisposing to HIV-Associated Neurocognitive Disorder

Cited by 41 publications

References 144 publications

Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders

Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders

Transcriptome analyses identify key cellular factors associated with HIV-1-associated neuropathogenesis in infected men

Hubungan Polimorfisme Gen Reseptor Estrogen Alfa Dengan Jumlah Sel T Cd4+ Pada Anak Terinfeksi Hiv

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