caa a22 4500 46790779X CHVBK 20180406152840.0 cr unu---uuuuu 170328e20060101xx s 000 0 eng 10.1007/s00251-005-0075-0 doi (NATIONALLICENCE)springer-10.1007/s00251-005-0075-0 Genetic variability in the extracellular matrix protein as a determinant of risk for developing HTLV-I-associated neurological disease [Elektronische Daten] [Yasuyuki Nobuhara, Koichiro Usuku, Mineki Saito, Shuji Izumo, Kimiyoshi Arimura, Charles Bangham, Mitsuhiro Osame] Aggrecan, which is a well-known proteoglycan in joint cartilage, also exists in the spinal cord and plays an important role in maintaining water content in the extracellular matrix structure. In this study, we first examined the variable number of tandem repeat (VNTR) polymorphism of the aggrecan gene in 227 HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, in 217 HTLV-I-infected healthy carriers (HCs), and in 85 normal controls. The VNTR allele 28 (1,630bp) was more frequently observed in HAM/TSP patients than in HCs (χ 2=12.02, p=0.0005, odds ratio 1.79, 95% C.I. 1.29-2.50) and in controls (χ 2=13.43, p=0.0002, odds ratio 2.54, 95% C.I. 1.52-4.25), although this allele was not related to disease progression or to HTLV-I provirus load. We also found that the aggrecan concentration in cerebrospinal fluid (CSF) from rapidly progressive HAM/TSP patients was significantly higher than in slowly progressive patients (corrected p=0.0145) but not in infected non-inflammatory neurological other disease controls (OND) (corrected p=0.078). We then analyzed this aggrecan VNTR polymorphism in the different set of patients with HAM/TSP (n=58) and healthy carriers (n=70). This analysis, again, revealed that allele 28 was detected more frequently in HAM/TSP group than in HCs (χ 2=11.03, p=0.0009, odd ratio 3.04, 95% C.I. 1.55-5.97). The reproducibility of our study was regarded as a second- or third-class association by comparing combined p values and the Better Associations for Disease and GEnes (BADGE) system. Our results suggest that aggrecan polymorphism can be a novel genetic risk factor for developing HAM/TSP. Springer-Verlag, 2006 Aggrecan nationallicence Extracellular matrix nationallicence HTLV-I nationallicence VNTR nationallicence HAM/TSP nationallicence Nobuhara Yasuyuki Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut Usuku Koichiro Department of Medical Information Science, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut Saito Mineki Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut Izumo Shuji Department of Molecular Pathology, Center for Chronic Viral Diseases, Kagoshima University, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut Arimura Kimiyoshi Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut Bangham Charles Department of Immunology, Imperial College School of Medicine at St Mary's, Norfolk Place, W2 1PG, London, United Kingdom aut Osame Mitsuhiro Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut Immunogenetics Springer-Verlag 57/12(2006-01-01), 944-952 0093-7711 57:12<944 2006 57 251 https://doi.org/10.1007/s00251-005-0075-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00251-005-0075-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nobuhara Yasuyuki Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut NATIONALLICENCE 700 1- Usuku Koichiro Department of Medical Information Science, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut NATIONALLICENCE 700 1- Saito Mineki Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut NATIONALLICENCE 700 1- Izumo Shuji Department of Molecular Pathology, Center for Chronic Viral Diseases, Kagoshima University, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut NATIONALLICENCE 700 1- Arimura Kimiyoshi Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut NATIONALLICENCE 700 1- Bangham Charles Department of Immunology, Imperial College School of Medicine at St Mary's, Norfolk Place, W2 1PG, London, United Kingdom aut NATIONALLICENCE 700 1- Osame Mitsuhiro Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 57/12(2006-01-01), 944-952 0093-7711 57:12<944 2006 57 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer