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

Abstract

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.

Keywords: Genetic association studies; HAM/TSP; Human T-cell leukemia virus 1; Linkage disequilibrium; SNP.