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 consent and the study approved by local ethics committee. PCR-RFLP method used for SNP typing. HTLV-I provirus load was measured by quantitative PCR. RESULTS: The IL-10 -592A/C SNP showed a significant difference in allele frequency between HAM/TSP patients and HCs (p=0.014). Possession of the IL-10 -592 A allele was associated with a >2-fold reduction in the odds of HAM/TSP (2p=0.011, OR=0.50). This effect remains significant even after taking into account the other two known predictors such as provirus load and HLA-A*02 genotype. Given the OR and the observed frequency of the IL-10 -592 A allele, we can estimate that IL-10 -592 A allele prevents 44.7%( 13.1%SD) of potential cases of HAM/TSP in the study population. The presence of the IL-10 592 A allele is also a significant predictor of lower provirus load in the entire cohort (p=0.001). Furthermore, HTLV-I Tax transactivates the IL-10 promoter in the human T-cell line Jurkat and this transactivation was higher with the IL-10 -592 C allele than the A allele. Among more than 90 non-HLA candidate gene loci we have so far examined, IL-10 -592 A/C SNP is the only non-HLA candidate gene locus associated with a significant reduction in both the provirus load and the risk of HAM/TSP. These data demonstrate that the IL-10 -592 A allele influences the provirus load in HTLV-I infected individuals, and defines a further component of the genetic susceptibility to HAM/TSP.
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.
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...متن کامل
Polygenic control of human T lymphotropic virus type I (HTLV-I) provirus load and the risk of HTLV-I-associated myelopathy/tropical spastic paraparesis.
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 کامل
Defective human T-cell lymphotropic virus type I (HTLV-I) provirus in 10 Chilean seronegative patients with tropical spastic paraparesis or HTLV-I-associated myelopathy.
We studied the presence of tax and ltr genes from human T-cell lymphotropic virus type I (HTLV-I) provirus in the peripheral blood mononuclear cells from 15 seronegative patients with tropical spastic paraparesis or HTLV-I-associated myelopathy by PCR. Only a region of the tax gene from 10 patients was amplified. The nucleotide homologies of six Chilean isolates to the ATK-1 clone ranged betwee...متن کامل
Human T-lymphotropic virus type I (HTLV-I) and tropical spastic paraparesis or HTLV-I-associated myelopathy in Hawaii.
Tropical spastic paraparesis or human T-lymphotropic virus type I (HTLV-I)-associated myelopathy is a degenerative encephalomyelopathy with pyramidal tract dysfunction affecting the lower extremities. It is associated with HTLV-I infection and found primarily in the Caribbean region and in southwestern Japan. Five cases of tropical spastic paraparesis (or HTLV-I-associated myelopathy) in Hawaii...متن کامل
دوره Volume 3 شماره Supplement 1
صفحات 84- 84
تاریخ انتشار 2010-11-20
با دنبال کردن یک ژورنال هنگامی که شماره جدید این ژورنال منتشر می شود به شما از طریق ایمیل اطلاع داده می شود.