A three-base-deletion polymorphism in the upstream non-coding region of human interleukin 7 (IL-7) gene could enhance levels of IL-7 expression

• Published in: International Journal of Immunogenetics Vol. 34; no. 2; pp. 107 - 113
• Main Authors: Song, H., Nakayama, E. E., Likanonsakul, S., Wasi, C., Iwamoto, A., Shioda, T.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2007; Wiley
• Subjects: Base Sequence; Codon, Initiator; Codon, Initiator - genetics; Codon, Initiator - physiology; Gene Expression Regulation; Gene Frequency; Genes, Reporter; Genotype; Humans; Interleukin-7; Interleukin-7 - genetics; Luciferases; Luciferases - genetics; Molecular Sequence Data; Polymorphism, Genetic; Protein Biosynthesis; Protein Biosynthesis - genetics; Sequence Deletion; Untranslated Regions; Untranslated Regions - genetics
• ISSN: 1744-3121; 1744-313X
• DOI: 10.1111/j.1744-313X.2007.00658.x

Summary Interleukin 7 (IL‐7) is a key factor in the survival, development and proliferation of B and T lymphocytes. Elevation of plasma IL‐7 has been reported in several lymphopenia cases such as HIV‐1 patients. After patients started to receive antiretroviral drugs and their CD4+ cell counts had recovered, IL‐7 in plasma decreased to normal levels. There are considerable variations in the levels of plasma IL‐7 as well as the rate of CD4+ T‐cell restoration. Although pre‐treatment plasma IL‐7 levels have been shown to be prognostic for the rate of post‐treatment CD4+ T‐cell restoration, the mechanisms responsible for the variations in plasma IL‐7 and rate of CD4+ T‐cell restoration are still completely unknown. In the study here, we searched for genetic polymorphisms that might affect levels of IL‐7 gene expression. For this purpose, we used 1658‐bp PCR‐amplified fragments of the IL‐7 gene containing 1470 bp of the upstream non‐coding region obtained from 151 Japanese and 234 Thai subjects. We found two novel human genetic polymorphisms in the upstream non‐coding region of the IL‐7 gene. The luciferase reporter assay demonstrated that one of those polymorphisms could increase the gene expression of IL‐7. We speculate that this polymorphism, a three base ATC deletion just upstream of an out‐of‐frame ATG codon in the upstream non‐coding region of the IL‐7 gene, reduces the efficiency of translation from the upstream, out‐of‐frame ATG, resulting in increased translation efficiency from the authentic ATG of IL‐7. Although the frequency of this allele is very low, it would be interesting to analyse this polymorphism in HIV‐1‐infected individuals with different rates of immune reconstitution after treatment with a highly active antiretroviral therapy.