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IL28B gene polymorphisms and all-cause mortality in HIV infected patients
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Reported by Jules Levin EACS 2011 Belgrade Serbia Oct 12-15
Milosz Parczewski, Magdalena Leszczyszyn-Pynka, Dorota Bander, Anna Urbanska, tukasz Socha,
Anna Boron-Kaczmarska
Department of Infectious Diseases and Hepatology, Pomeranian Medical Univeristy, Szczecin, Poland
IL28B is ifn lambda The signalling pathway of type III interferons (IFNs) compared with type II and type I IFNs. IFNλ binds the IFNλR1 chain leading to a conformational change in the receptor. It recruits a second short receptor chain (IL10R2). JAK 1 and Tyk 2 transphosphorylate the receptor chains and form phosphorylated tyrosine peptides on the IFNλR1 receptor chain. STAT proteins bind and are phosphorylated. They can then form homo- or heterodimers and migrate to the nucleus to bind gene regulatory elements (gamma-activated sequences, GAS). In the case of type I and type III IFNs, they can also bind interferon regulatory factor 9 (IRF9) in the cytoplasm and then migrate to the nucleus to bind interferon stimulated regulatory elements (ISREs) to regulate gene transcription.
Studies so far have concentrated on the IL28 gene variants associated treatment spontaneous clearance and treatment response in HCV, with identification of the response" associated variants and minority, non-response alleles and genotypes. This is now a common knowledge.
Il28B single nucleotide variants are associated with of the interferon λ levels, changes in the HCV-RNA serum levels and HIV-RNA set point prior to antiretroviral therapy (cART).
Interferon λ induces the expression of chemokine receptors on macrophages and dendritic cells stimulating synthesis of the virus restriction factors.
Il28B single nucleotide variants are associated with of the interferon λ levels, changes in the HCV-RNA serum levels and HIV-RNA set point prior to antiretroviral therapy (cART).
The association between IL28 CC genotype and decreased survival probability for the antiretroviral treated individuals remained significant after adjustment for gender, baseline CD4 count, CDC category at HIV diagnosis (asymptomatic vs. symptomatic) and age (multivariate HR 1.75, 95%CI: 1.20-2.30, p=0.047).
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