CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection

Suppiah, Vijayaprakash; Armstrong, Nicola J.; O'Connor, K.; Berg, Thomas; Weltman, Martin; Abate, Maria Lorena; Spengler, Ulrich; Bassendine, Margaret F.; Dore, Gregory J.; Irving, William L.; Powell, Elizabeth E.; Nattermann, Jacob; Müller, Tobias; Riordan, Stephen M.; Stewart, Graeme J.; George, Jacob; Booth, David R.; Ahlenstiel, Golo; Michalk, M.; Malik, Barbara; McClure, C. Patrick; Smith, Sherie; Sheridan, David; Snape, Elizabeth; Fragomeli, Vincenzo; Norris, Richard H.; How-Chow, D.; Jonsson, Julie R.; Barrie, H; Stelzer-Braid, Sacha; Fletcher, Shona; Applegate, Tanya; Grebely, Jason; Matthews, Gail; Bharadwaj, Mandvi; Smedile, Antonina

doi:10.1038/gene.2013.15

Cited by 4 publications

(1 citation statement)

References 41 publications

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“…Our results show that this CCR5 polymorphism did not play any significant role in the anti-HCV treatment response, while at the same time confirming the very well known role played by severe fibrosis, older age, higher pretreatment HCV RNA, genotype 2 and 3 and IFNL3/4 genetic polymorphisms. As already known, the latter are currently the strongest host genetic markers to predict IFN-alpha-based treatment-induced HCV clearance, and, as demonstrated in a recent and large serie of 813 Caucasian patients with chronic hepatitis C genotype 1 [27], CCR5delta32 did not improve prediction of SVR in the context of the IFNL3 polymorphisms. These results match those of previous, smaller series [28]–[31], but appear in conflict with those of an early study which had identified CCR5delta32 carriage as an independent negative predictor for the end of treatment virological response to the less potent IFN-alpha monotherapy [30].…”

Section: Discussionmentioning

confidence: 91%

Clinical Significance of the CCR5delta32 Allele in Hepatitis C

Morard¹,

Clément²,

Calmy³

et al. 2014

PLoS ONE

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BackgroundThe CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection.Methods CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance.ResultsCarriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35–0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99–1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4).ConclusionsThe CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.

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Section: Discussionmentioning

confidence: 91%

Clinical Significance of the CCR5delta32 Allele in Hepatitis C

Morard¹,

Clément²,

Calmy³

et al. 2014

PLoS ONE

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Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

et al. 2020

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The interactions between chemokine receptors and their ligands may affect susceptibility to infectious diseases as well as their clinical manifestations. These interactions mediate both the traffic of inflammatory cells and virus-associated immune responses. In the context of viral infections, the human CC chemokine receptor type 5 (CCR5) receives great attention from the scientific community due to its role as an HIV-1 co-receptor. The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. Also, the genetic variant CCR5Δ32 modifies the CCR5-mediated inflammatory responses in various conditions, such as inflammatory and infectious diseases. CCR5 antagonists mimic, at least in part, the natural effects of the CCR5Δ32 in humans, which explains the growing interest in the potential benefits of using CCR5 modulators for the treatment of different diseases. Nevertheless, beyond HIV infection, understanding the effects of the CCR5Δ32 variant in multiple viral infections is essential to shed light on the potential effects of the CCR5 modulators from a broader perspective. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. Subsequently, this review addresses the impacts of CCR5 gene editing and CCR5 modulation on health and viral diseases. Also, this article connects recent findings regarding extracellular vesicles (e.g., exosomes), viruses, and CCR5. Neglected and emerging topics in "CCR5 research" are briefly described, with focus on Rocio virus, Zika virus, Epstein-Barr virus, and Rhinovirus. Finally, the potential influence of CCR5 on the immune responses to coronaviruses is discussed.

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Genetic variants in chemokine CC subfamily genes influence hepatitis C virus viral clearance

et al. 2018

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Chemokine genes may influence both hepatitis C virus (HCV) spontaneous clearance in acute infection and treatment response in chronic infection. We conducted this study to evaluate whether the genetic variants in several CC family genes influence HCV spontaneous clearance and treatment response. The current research genotyped eight SNPs, including CCR1 rs3733096, rs13096371, CCR5 rs746492, rs1800874, CCL3 rs1130371, CCL5 rs3817656, CCL8 rs1133763, CCL14 rs854625, to explore their associations with HCV spontaneous clearance and response to treatment in two populations. We identified that the CCR1 rs3733096 (dominant model: adjusted OR = 2.29, 95% CI = 1.49-3.53, additive model: adjusted OR = 2.21, 95% CI = 1.50-3.25) and CCL5 rs3817656 (dominant model: OR = 1.37, 95% CI = 1.10-1.70, additive model: OR = 1.33, 95% CI = 1.12-1.58) were associated with HCV spontaneous clearance in Chinese Han population, while we found no association with treatment response. Moreover, the expression quantitative trait loci (eQTL) analysis showed that the risk alleles of rs3817656 were significantly associated with downregulated expression of CCL5 in whole blood (P < 0.001). The polymorphism of CCR1 rs3733096 and CCL5 rs3817656 are associated with spontaneous clearance of HCV in Chinese Han population.

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CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection

Cited by 4 publications

References 41 publications

Clinical Significance of the CCR5delta32 Allele in Hepatitis C

Clinical Significance of the CCR5delta32 Allele in Hepatitis C

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

Genetic variants in chemokine CC subfamily genes influence hepatitis C virus viral clearance

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