Novel variants of human IFN-alpha detected in tumor cell lines and biopsy specimens
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
Authors: Golovleva, I; Biasotto, M; Verpy, E; Roos, G; Meo, T; Tosi, M; Lundgren, E
Abstract
Interferon-alpha constitutes a complex gene family with 14 genes clustered on the short arm of chromosome 9. More than 50 sequence variants have been described, However, an extensive genetic polymorphism has not been seen in the few population studies reported so far, As many of the sequence variants reported were derived from tumor cell lines, we have investigated whether IFN-alpha genes are unstable in tumor cells, Using fluorescence-assisted mismatch analysis (FAMA), combined with allele-specific primer extension, RFLP analysis, and direct sequencing, we detected in a panel of 14 tumor cell lines two new sequence variants of the IFNA1 and IFNA13 genes, Further two-paint mutations were found in tumor samples from leukemias (n = 10) and renal cell carcinomas (n = 17) not seen in normal tissues, In the IFNA17 gene, three new sequence variants were detected, one in a tumor cell line and two in tumor biopsy specimens, Besides these individual point mutations, two new polymorphisms were found in each of the IFNA13 and IFNA17 genes, No new variants were found in the IFNA2 and IFNA10 genes, The results suggest that new sequence variants of the IFN-alpha genes occur relatively frequently in tumors or in tumor cell lines.
Relationship between IFNA1, IFNA5, IFNA10, and IFNA17 gene polymorphisms and Crimean-Congo hemorrhagic fever prognosis in a Turkish population range
JOURNAL OF MEDICAL VIROLOGY
Authors: Elaldi, Nazif; Yilmaz, Meral; Bagci, Binnur; Yelkovan, Izzet; Bagci, Gokhan; Gozel, Mustafa Gokhan; Engin, Aynur; Bakir, Mehmet; Dokmetas, Ilyas
Abstract
Crimean-Congo hemorrhagic fever (CCHF) is a fatal emerging acute viral infection. Not much is known regarding the pathogenic mechanisms and the reasons behind severe or mild disease courses in CCHF. IFN-alpha (IFNA) is one of the essential cytokines in the immune system. Existence of single nucleotide gene polymorphisms (SNPs) in cytokines can cause susceptibility or resistance to viral agents and different clinical courses. Hence, the relationship between SNPs in genes encoding cytokines (IFNA1 -1823G/A (rs1332190), IFNA5 -2529T/A (rs758236), IFNA10 Cys20stop (rs10119910), and IFNA17 Ile184Arg (rs9298814) SNPs and disease susceptibility were investigated. The associations between SNPs and CCHF prognosis were also studied. Total 150 patients with CCHF and 170 healthy individuals were enrolled. Genotyping was performed by PCR-RFLP methods. The frequency of IFNA1 -1823 (rs1332190) GG genotype was significantly higher in control subjects than CCHF patients (20% vs. 8%; P=0.01). For IFNA17 Ile184Arg (rs9298814) polymorphism, CCHF patients having TG genotype had a higher frequency than the control subjects (38% vs. 32.4%; P=0.039). The distribution of TT+TG genotype frequencies was also significantly higher in CCHF group than the controls (97.3% vs. 91.8%; P=0.049). Genotype and allele frequencies for IFNA subtypes between fatal and survivors were the same (P>0.05). Genotype and allele frequencies between severe and mild/moderate CCHF patients were also the same (P>0.05). The results show that IFNA1 rs1332190 and IFNA17 rs9298814 SNPs may play an important role in CCHF susceptibility. Determining the existence of other connections for IFNA SNPs and CCHF severity and fatality requires further investigations. J. Med. Virol. 88:1159-1167, 2016. (c) 2015 Wiley Periodicals, Inc.