Association of a novel single nucleotide polymorphism in the human perforin gene with the outcome of HTLV-I infection in patients from northeast Iran (Mash-had).

Human T lymphotropic virus I (HTLV-I)-specific cytotoxic T lymphocytes (CTL) recognize the products of the HTLV-I Tax, in the context of HLA-A2 and kill their target through a perforin-dependent mechanism. The efficiency of the CTL response may lead HTLV-I-infected individuals to remain carriers or to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Perforin is a cytolytic molecule that contributes to CTL-mediated killing of virus-infected cells. Thus polymorphism in the perforin gene may determine the efficiency of the CTL response in HTLV-I-infected individuals. In this study, we performed single-stranded conformational polymorphism (SSCP) and DNA sequencing to analyze the promoter, 5' UTR and first intron of the perforin gene to identify novel polymorphisms. We detected a novel polymorphism in the first intron at position +418*C/T, relative to the transcription start site. Genotyping of patients with HAM/TSP, HTLV-I carriers, and healthy controls revealed that the frequency of the C allele was statistically significantly increased in HAM/TSP patients compared with healthy controls group (p = 0.005). The frequency of the C allele was higher, but not significantly so, in the HAM/TSP group compared with HTLV-I carriers (p = 0.09), whereas there was no difference between HTLV-I carriers and healthy controls. Our results suggest that the perforin +418*C/T polymorphism is associated with the outcome of HTLV-I infection.