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 39 non-HLA candidate gene loci, 3 new host genetic factors that influenced the risk of HAM/TSP or the provirus load of HTLV-I were identified. The promoter TNF -863A allele predisposed to HAM/TSP, whereas SDF-1 +801A 3'UTR, and IL-15 191C alleles conferred protection. Knowledge of HTLV-I-infected individuals' ages, sex, provirus load, HTLV-I subgroup, and genotypes at the loci HLA-A, HLA-C, SDF-1, and TNF-alpha allowed for the correct identification of 88% of cases of HAM/TSP in this Japanese cohort.
Vine
Alison M
AM
Department of Immunology, Imperial College Faculty of Medicine, St. Mary's Campus, London, United Kingdom.
Witkover
Aviva D
AD
Lloyd
Alun L
AL
Jeffery
Katie J M
KJ
Siddiqui
Asna
A
Marshall
Sara E F
SE
Bunce
Mike
M
Eiraku
Nobutaka
N
Izumo
Shuji
S
Usuku
Koichiro
K
Osame
Mitsuhiro
M
Bangham
Charles R M
CR
D000483:Alleles; D002353:Carrier State / Q000276:immunology / Q000821:virology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification*; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics; D007564:Japan; D020412:Multifactorial Inheritance; D015493:Paraparesis, Tropical Spastic / Q000235:genetics / Q000276:immunology / Q000821:virology*; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000302:isolation & purification*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019562:Viral Load
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015234:HLA-A Antigens; D015236:HLA-C Antigens; D019409:Interleukin-15; D014409:Tumor Necrosis Factor-alpha