Longer dinucleotide repeat polymorphism in matrix metalloproteinase-9 (MMP-9) gene promoter which correlates with higher HTLV-I Tax mediated transcriptional activity influences the risk of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP).
Matrix metalloproteinase-9 (MMP-9) has been reported to be expressed in various inflammatory disorders including human T cell lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-I-infected T-cells expressed high levels of MMP-9 via viral transactivator Tax mediated activation of the MMP-9 promoter. To investigate whether the d(CA) repeat polymorphism in MMP-9 promoter affects the risk of developing HAM/TSP, we compared the allele frequencies between 200 HAM/TSP patients and 200 HTLV-I seropositive asymptomatic carriers (HCs). The longer d(CA) repeat alleles of MMP-9 promoter, which was associated with higher Tax-mediated transcriptional activity, was more frequently observed in HAM/TSP patients than HCs (p<0.01 by Mann-Whitney U-test). The length alteration of this d(CA) repeat in the MMP-9 promoter may cause phenotypic differences among HTLV-I infected infiltrating cells and may thereby be in part responsible for the development of HAM/TSP.
Kodama
Daisuke
D
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Saito
Mineki
M
Matsumoto
Wataru
W
Sabouri
Amir H
AH
Izumo
Shuji
S
Arimura
Kimiyoshi
K
Usuku
Koichiro
K
Bangham
Charles R M
CR
Osame
Mitsuhiro
M
D000328:Adult; D018900:Dinucleotide Repeats / Q000235:genetics*; D016356:Gene Products, tax / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D016356:Gene Products, tax; D020780:Matrix Metalloproteinase 9