Delimitation of the upstream region of NFKBIA gene associated with HTLV-1-associated myelopathy/tropical spastic paraparesis using candidate Tag-SNPs in Peruvian HTLV-1 infected individuals

Delimitation of the upstream region of NFKBIA gene associated with HTLV-1-associated myelopathy/tropical spastic paraparesis using candidate Tag-SNPs in Peruvian HTLV-1 infected individuals

In Peru, it is estimated that about 150 000-400 000 people carry the Human T-lymphotropic virus 1 (HTLV-1). Only 10% of HTLV-1 carries develop complications related to HTLV-1. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic disabling inflammatory disease affecting th...

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Bibliographic Details
Published in:Infection, genetics and evolution Vol. 75; p. 103929
Main Authors: Posadas, A.E., Rosado, J.J., Gotuzzo, E., Talledo, M.J.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01-11-2019
Subjects:
Adult
Case-Control Studies
Female
Genetic association studies
Genetic Predisposition to Disease
HAM/TSP
HTLV-I Infections - genetics
Human T-cell leukemia virus 1
Humans
Linkage Disequilibrium
Male
Middle Aged
NF-KappaB Inhibitor alpha - genetics
Paraparesis, Tropical Spastic - virology
Peru
Polymorphism, Single Nucleotide
SNP
Viral Load
Peru
Human T-cell leukemia virus 1
Genetic association studies
HAM/TSP
SNP
Linkage disequilibrium
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Summary:In Peru, it is estimated that about 150 000-400 000 people carry the Human T-lymphotropic virus 1 (HTLV-1). Only 10% of HTLV-1 carries develop complications related to HTLV-1. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic disabling inflammatory disease affecting the spinal cord. HAM/TSP produces principally weakness in the lower limbs and bladder disturbances, among other complications. In a previous study, our group identified three SNPs (rs3138053, rs2233406, and rs3138045) located in the promoter region of the NFKBIA gene associated with HAM/TSP. This study aimed to analyze the association between four Tag-SNPs (rs10148482, rs17103274, rs17103282, and rs762009) located in the upstream region of the NFKBIA gene and HAM/TSP, and to delimit the linkage disequilibrium zone in the upstream region of the NFBKIA gene associated with HAM/TSP. The tetra-primers ARMS-PCR technique was used to genotype 4 Tag-SNPs on 140 HAM/TSP patients and 258 asymptomatic carriers. The SNP rs17103282 showed a deviation from Hardy-Weinberg equilibrium (p < .0001). Neither of three Tag-SNPs showed an association with HAM/TSP (P > .05). No linkage disequilibrium between four Tag-SNPs evaluated in this study and previous ones was observed. Here we show the region located in the upstream region of the NFKBIA gene highly associated with HAM/TSP disease in patients infected with HTLV-1 from Lima, Peru. •SNPs in the promoter region of NFKBIA gene predisposed to disease susceptibility.•Linkage disequilibrium analysis determine the NFKBIA region associated with HAM/TSP.•Proviral load remains as the principal factor associated to HAM/TSP disease.
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ISSN:1567-1348
1567-7257
DOI:10.1016/j.meegid.2019.103929