Low-density lipoprotein receptor genotyping enhances the predictive value of IL28B genotype in HIV/hepatitis C virus-coinfected patients

Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain.
AIDS (London, England) (Impact Factor: 5.55). 05/2011; 25(11):1415-20. DOI: 10.1097/QAD.0b013e328348a7ac
Source: PubMed


The aims of this study were to appraise the predictive value of variations in a single-nucleotide polymorphism (SNP) in the low-density lipoprotein receptor (LDLR) gene for sustained virological response (SVR) to pegylated interferon (Peg-IFN) and ribavirin (RBV), as well as to analyze the relationship between LDLR genotype and other predictors of SVR, particularly IL28B genotype, in patients coinfected with HIV and hepatitis C virus (HCV).
One hundred and eighty-four HIV/HCV-coinfected, treatment-naive patients with chronic HCV infection, who received Peg-IFN and RBV, were included. Variations in the SNP rs14158 and rs12979860 were tested by Taqman PCR assay.
Twenty-eight (38%) patients with rs14158 TT/TC and 61 (55%) with CC (P = 0.028) achieved SVR. The rates of SVR in patients with rs14158 TT/TC and with CC harboring HCV 1-4 were 20 and 41% (P = 0.020), respectively, and, in those with HCV genotype 2-3, 75 and 84% (P = 0.513), respectively. Patients with rs14158 CC showed less commonly plasma HCV-RNA load at least 600000 IU/ml (57 vs. 71%, P = 0.047) and lower likelihood of relapse (13 vs. 30%, P = 0.023). In patients with HCV genotype 1-4, the rates of SVR according to the combination of IL28B/LDLR genotypes were: CC/CC = 69%; CC/non-CC: 30%; non-CC/CC: 25%; non-CC/non-CC: 14% (P < 0.001).
Variations in rs14158 are associated with SVR to Peg-IFN and RBV in HIV/HCV-coinfected patients harboring HCV genotype 1-4. LDLR and IL28B genotypes seem to have a synergistic effect on SVR. The combined use of LDLR and IL28B genotypes in routine clinical practice could enhance the predictive value of IL28B genotype alone.

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    • "However, the association between interferon-stimulated gene (ISG) expression and the IL28B genotype is a controversial point [6]. This suggests that there may be other factors that modify the effect of the IL28B genotype on HCV treatment response [7], [8]. "
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    ABSTRACT: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR) 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6). Rapid and sustained virological response (RVR and SVR) rates were also analyzed. Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week1: p = 0.01; week2: p = 0.038; week 4: p = 0.03). Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031). With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week1: p<0.001; week2: p = 0.01; week 4: p = 0.02), RVR (p = 0.015) and SVR (p = 0.029) than those not carrying KIR3DS1. Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.
    Full-text · Article · Apr 2013 · PLoS ONE
    • "One of these SNPs, rs12979860, was pivotal in predicting the resolution of HCV-1 infections (Thomas et al., 2009). Little is known about the IFN l family, but evidence is increasing to support a role for them in the immune response to viral infections (Chevaliez and Hezode, 2010; Pineda et al., 2011). Results of a GWAS showed a significant association between treatment responses with SNP rs12980275 located in the IL28B gene region (Venegas et al., 2011). "
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    ABSTRACT: Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by thrombocytopenia with or without mucocutaneous bleeding manifestations. ITP patients have significant defects in immune self-tolerance: autoreactive T-lymphocyte clones are capable of directly damaging platelets and possibly megakaryocytes and are likely to proliferate under the influence of Th lymphocytes. The CB2 receptor is thought to be the principal cannabinoid receptor that mediates immune modulation by endocannabinoid. The later has shown a complex range of immunomodulatory effects, primarily suppressive effects on leukocytes and immune functions, including modulation of Th cell development, chemotaxis and cytokine secretion. In this study, we investigated the association between cannabinoid CB2 receptor gene (CNR2) Q63R polymorphism and the susceptibility to childhood ITP in Egyptian population. CNR2 genotyping in ITP patients revealed that 41% of patients had the QR(AA/GG) heterotype and 49% had the RR(AA/AA) homotype. There was a significantly higher frequency of homomutant genotype (RR) in ITP patients than in controls, which conferred more than two-fold increased risk of ITP among Egyptian children [odds ratio (OR) 2.352, 95% confidence interval (CI) 1.313-4.215]. There was a significant statistical difference in the distribution of CNR2 Q63R genotypes between chronic ITP patients group and the control groups. The homomutant genotype carried nearly three-fold increased risk for chronic ITP (OR 2.701, 95% CI 1.462-5.009). In conclusion, CNR2 Q63R polymorphism may represent a novel genetic risk factor in the pathophysiology of chronicity development of ITP in Egyptian children.
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