title: 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.
abstract: 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.
authors: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. hhsong@biken.osaka-u.ac.jp
authors: H
authors: H
authors: Song
authors: E E
authors: EE
authors: Nakayama
authors: S
authors: S
authors: Likanonsakul
authors: C
authors: C
authors: Wasi
authors: A
authors: A
authors: Iwamoto
authors: T
authors: T
authors: Shioda
mesh_terms: D001483:Base Sequence; D018387:Codon, Initiator / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D005787:Gene Frequency; D017930:Genes, Reporter; D005838:Genotype; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D014176:Protein Biosynthesis / Q000235:genetics*; D017384:Sequence Deletion; D020506:Untranslated Regions / Q000235:genetics*
chemical_list: D018387:Codon, Initiator; D015851:Interleukin-7; D020506:Untranslated Regions; D008156:Luciferases