Polymorphism in the interleukin-10 promoter affects both provirus load and the risk of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.
نویسندگان
چکیده
To investigate non-human leukocyte antigen candidate genes that influence the outcome of human T cell lymphotropic virus (HTLV) type I infection, we analyzed 6 single-nucleotide polymorphisms in the interleukin (IL)-10 promoter region in 280 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 255 HTLV-I-seropositive asymptomatic carriers from an area where HTLV-I is endemic. The IL-10 -592 A allele, which shows lower HTLV-I Tax-induced transcriptional activity than the C allele in the Jurkat T cell line, was associated with a >2-fold reduction in the odds of developing HAM/TSP (P=.011; odds ratio [OR], 0.50 [95% confidence interval, 0.30-0.86]) by reducing the provirus load in the whole cohort (P=.009, analysis of variance). Given the OR and the observed frequency of IL-10 -592 A, we demonstrate that this allele prevents approximately 44.7% (standard deviation, +/-13.1%) of potential cases of HAM/TSP, which indicates that it defines one component of the genetic susceptibility to HAM/TSP in the cohort.
منابع مشابه
Polymorphism in the interleukin-10 promoter affects both provirus load and the risk of human t lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis
To investigate candidate genes that influence the risk of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), we analyzed 6 single nucleotide polymorphisms (SNP) in the interleukin-10 (IL-10) promoter region. METHODS: 280 cases of HAM/TSP patients and 255 HTLV-I seropositive asymptomatic carriers (HCs) from Kagoshima, Japan were studied. All subjects gave written informed conse...
متن کاملPolymorphism in the interleukin-10 promoter affects both provirus load and the risk of human t lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis
To investigate candidate genes that influence the risk of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), we analyzed 6 single nucleotide polymorphisms (SNP) in the interleukin-10 (IL-10) promoter region. METHODS: 280 cases of HAM/TSP patients and 255 HTLV-I seropositive asymptomatic carriers (HCs) from Kagoshima, Japan were studied. All subjects gave written informed conse...
متن کاملThe Impact of Immune Response on HTLV-I in HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)
Human T lymphotropic virus type I (HTLV-I) is a retrovirus which is associated with adult T cells leukaemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of HTLV-I-infected individuals. It is not clear why a minority of HTLV-I-infected individuals develop HAM/TSP and majority remains lifelong carriers. It seems that the interaction between the v...
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Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is one outcome of infection with HTLV-I. A population association study of 229 patients with HAM/TSP and 202 healthy carriers of HTLV-I in southern Japan showed that this outcome of HTLV-I infection and the HTLV-I provirus load are under polygenic control. Of 58 polymorphic sites studied in 3...
متن کاملAssociation of IL-10 Gene Polymorphisms and Human T Lymphotropic Virus Type I-Associated Myelopathy/tropical Spastic Paraparesis in North-East of Iran (Mashhad)
The underlying mechanisms leading to the development of human T-cell lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-I infected individuals are not fully understood. Host genetic factors appear to be involved as risk factors for developing HAM/TSP. We investigated the possible contribution of interleukin-10 (IL-10) as a risk factor to HA...
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ورودعنوان ژورنال:
- The Journal of infectious diseases
دوره 190 7 شماره
صفحات -
تاریخ انتشار 2004