Human genetic variation in HIV disease

McLaren, Paul J.; Fellay, Jacques

doi:10.1097/coh.0000000000000133

Cited by 10 publications

(6 citation statements)

References 22 publications

(16 reference statements)

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“…Despite this, this is the first time that a NR1I2 gene polymorphism was found to be related to time of progression to AIDS and even though our sample was not an extensive representative, it can be hypothesized that the absence of the rs7643645 SNP in homozygosis (presence of the A allele) is associated with a delayed progression towards AIDS, when also considering ethnicity and gender. This agrees with the widely accepted belief of several different factors influencing AIDS progression and illustrates the importance of considering them all together (McLaren & Fellay 2015). In addition, this finding is in accordance to several recent studies that suggest a role of NR in immune mechanisms and HIV infection.…”

Section: Discussionsupporting

confidence: 91%

Association of NR1I2 gene polymorphisms and time of progression to AIDS

Medeiros

Menti

Benelli

et al. 2017

Mem. Inst. Oswaldo Cruz

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BACKGROUND The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS.OBJECTIVE To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients.METHODS Blood samples were obtained from 96 HIV-1 positive individuals following informed consent. DNA was isolated and genotyped through real time polymerase chain reaction (PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic features and behaviors were answered and time of progression to AIDS was estimated based on medical chart analysis.FINDINGS Patients with the GG genotype for rs7643645 were shown to be related with a more rapid disease progression when compared to GA and AA genotypes. This result was maintained by the Multivariate Cox Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and CCR5del32 polymorphisms.MAIN CONCLUSIONS Recent studies reported the expression of the nuclear receptors in T-Lymphocytes, suggesting their possible role in the immune response. In addition, nuclear receptors have been shown to inhibit the HIV replication, although no such mechanism has been thoroughly elucidated to date. This is the first time an association between NR1I2 polymorphism and time of progression to AIDS is reported and supports an apparent relationship between the gene in the immune response and identifies another genetic factor influencing AIDS progression.

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Section: Discussionsupporting

confidence: 91%

Association of NR1I2 gene polymorphisms and time of progression to AIDS

Medeiros

Menti

Benelli

et al. 2017

Mem. Inst. Oswaldo Cruz

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“…Based on previous human genetic studies across Africa (Cao et al, 2004, Paximadis et al, 2012, Kijak et al, 2009, McLaren and Fellay, 2015, McLaren and Carrington, 2015) (www.allelefrequencies.net/), we now know that the Bantu population has the greatest genetic diversity of Homo sapiens . Low prevalence of “HIV protective” polymorphisms/alleles in the Shona and Buganda tribes (both Bantu) (e.g.…”

Section: Discussionmentioning

confidence: 99%

Infecting HIV-1 Subtype Predicts Disease Progression in Women of Sub-Saharan Africa

et al. 2016

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IntroductionLong-term natural history cohorts of HIV-1 in the absence of treatment provide the best measure of virulence by different viral subtypes.MethodsNewly HIV infected Ugandan and Zimbabwean women (N = 303) were recruited and monitored for clinical, social, behavioral, immunological and viral parameters for 3 to 9.5 years.ResultsUgandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D (GEE model, P < 0.001), a difference not associated with any other clinical parameters. Relative replicative fitness and entry efficiency of HIV-1 variants directly correlated with virulence in the patients, subtype D > A > C (P < 0.001, ANOVA).DiscussionHIV-1 subtype C was less virulent than either A or D in humans; the latter being the most virulent. Longer periods of asymptomatic HIV-1 subtype C could explain the continued expansion and dominance of subtype C in the global epidemic.

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“…Measured during the chronic phase of infection, the viral load (referred to as setpoint viral load, spVL) exhibits large variation in a population. Several studies have been carried out to elucidate whether this variation is primarily driven by host genetics [1][2][3][4] , viral genetics [5][6][7][8][9] , or environmental effects 7 . Genome-wide association studies consistently show that amino acid polymorphisms in the peptide binding groove of the HLA-A and HLA-B proteins are associated with the viral load of an individual.…”

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confidence: 99%

Estimating the respective contributions of human and viral genetic variation to HIV control

Bartha

McLaren

Brumme

et al. 2015

Preprint

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We evaluated the fraction of variation in HIV-1 set point viral load attributable to viral or human genetic factors by using joint host/pathogen genetic data from 541 HIV infected individuals. We show that viral genetic diversity explains 29% of the variation in viral load while host factors explain 8.4%. Using a joint model including both host and viral effects, we estimate a total of 30% heritability, indicating that most of the host effects are reflected in viral sequence variation.

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Human genetic variation in HIV disease

Cited by 10 publications

References 22 publications

Association of NR1I2 gene polymorphisms and time of progression to AIDS

Association of NR1I2 gene polymorphisms and time of progression to AIDS

Infecting HIV-1 Subtype Predicts Disease Progression in Women of Sub-Saharan Africa

Estimating the respective contributions of human and viral genetic variation to HIV control

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