Both Variant Forms of Interferon-α4 Gene (IFNA4a and IFNA4b) Are Present in the Human Population

Abstract

Alpha interferons (IFN-α) are a class of cytokines with various activities that are used as therapeutic agents for treatment of cancer and viral and immune disorder diseases. At least 13 IFN-α genes and 1 IFN-α pseudogene have been identified, which are clustered on human chromosome 9. Among the known IFN-α species, a number of allelic variants have been reported. Two variants of IFN-α4 (IFN-α4a and IFN-α4b) are known, which differ from each other by changes in their coding regions at nucleotide positions 220 and 410 and can be distinguished by selective restriction enzyme analysis. We have developed oligonucleotide primers for specific amplification of IFN-α4 gene fragments using the polymerase chain reaction (PCR). Genomic DNA obtained from over 28,000 normal healthy individuals and six human cell lines were used in this study. The resulting PCR products were analyzed by restriction endonuclease digestion and DNA sequencing to identify the presence of variant sequences. The results show that the DNA sequences for both variants of IFN-α4 are found in the population in nearly equal proportion. Individuals with either homozygous (e.g., α4a/α4a or α4b/α4b) or heterozygous (i.e., α4a/α4b) IFN-α4 genes were detected. Among the cell lines, KG-1, EB-3, and HTB-10 cells contain the genes for IFN-α4a only, whereas U-937, Namalwa, and Daudi cells contain the genes for both IFN-α4a and IFN-α4b.