Journal of Medical Virology 84:319–326 (2012) Possible Implication of NFKB1A and NKG2D Genes in Susceptibility to HTLV-1-Associated Myelopathy/ Tropical Spastic Paraparesis in Peruvian Patients Infected With HTLV-1 Michael Talledo, 1,2,3 * Giovanni Lo ´ pez, 1 Jeroen R. Huyghe, 2,3 Kristien Verdonck, 1,4 Elsa Gonza ´ lez, 1,5 Daniel Clark, 1,6 Guido Vanham, 4,7 Eduardo Gotuzzo, 1,5,8 Guy Van Camp, 2,3 and Lut Van Laer 2,3 1 Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru 2 Department of Medical Genetics, University of Antwerp, Antwerp, Belgium 3 Department of Medical Genetics, University Hospital of Antwerp, Antwerp, Belgium 4 Virology Unit, Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium 5 Facultad de Medicina, Universidad Peruana Cayetano Heredia, Lima, Peru 6 Facultad de Ciencias y Filosofı´a, Laboratorios de Investigacio´n y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Peru 7 Department of Biomedical Sciences, University of Antwerp, Antwerp-Belgium 8 Hospital Cayetano Heredia, Lima, Peru The human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV-1- associated myelopathy/tropical spastic parapa- resis (HAM/TSP), a progressive disease causing paraparesis of the lower limbs. Only a minority of persons infected with HTLV-1 develop HAM/ TSP. Universal susceptibility factors for HAM/ TSP are not known. The viral genotype is simi- lar in asymptomatic carriers and HAM/TSP patients. High proviral load has been associat- ed consistently with HAM/TSP, but this factor does not explain fully the presence of disease in HTLV-1-infected subjects. Most likely, host genetic factors will play an important role in HAM/TSP development. A two-stage case- control study was carried out to evaluate the association between HAM/TSP and candidate single nucleotide polymorphisms (SNPs) from 45 genes in addition to six human leukocyte antigen (HLA) alleles. Ancestry-informative markers were used to correct for population stratification. Several SNPs belonging to NFKB1A and NKG2D showed a trend of associ- ation in both stages. The fact that the direction of the association observed in the first stage was the same in the second stage suggests that NFKB1A and NKG2D may be implicated in the development of HAM/TSP. Further repli- cation studies in independent HTLV-1 patient groups should validate further these associa- tions. J. Med. Virol. 84:319–326, 2012. ß 2011 Wiley Periodicals, Inc. KEY WORDS: human T-cell lymphotropic virus 1; tropical spastic para- paresis; tropical spastic; Peru; genetic association studies INTRODUCTION Human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus to be discovered. HTLV-1 infects approximately 20 million people around the world [de The ´ and Bomford, 1993]. Although this virus has a worldwide distribution, Additional supporting information may be found in the online version of this article. Abbreviations: HTLV-1, human T-lymphotropic virus 1; HAM/ TSP, HTLV-1-associated myelopathy/tropical spastic parapare- sis; NKG2D, killer cell lectin-like receptor subfamily K, member 1; NFKB1A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; ATL, adult T-cell leukemia/lymphoma. Conflicts of interest: None. This study was partially presented at the Colloquium on Neglected Tropical Diseases of Latin America, Lima, Peru from November 12 to 14, 2009. *Correspondence to: Michael Talledo, Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Caye- tano Heredia, Lima, Peru. E-mail: michaeltalledo@yahoo.com Accepted 13 September 2011 DOI 10.1002/jmv.22255 Published online in Wiley Online Library (wileyonlinelibrary.com). ß 2011 WILEY PERIODICALS, INC.