title: 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).
abstract: 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.
authors.affiliation: Immunology Research Group, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Houshang
authors.initials: H
authors.lastname: Rafatpanah
authors.forename: Vera
authors.initials: V
authors.lastname: Pravica
authors.forename: Reza
authors.initials: R
authors.lastname: Farid
authors.forename: Mohammed Reza
authors.initials: MR
authors.lastname: Abbaszadegan
authors.forename: Abbas
authors.initials: A
authors.lastname: Tabatabaei
authors.forename: Abbas
authors.initials: A
authors.lastname: Goharjoo
authors.forename: Mohammed Mehdi
authors.initials: MM
authors.lastname: Etemadi
authors.forename: Ian V
authors.initials: IV
authors.lastname: Hutchinson
mesh_terms: D016172:DNA Fingerprinting; D005787:Gene Frequency; D015490:HTLV-I Infections / Q000175:diagnosis / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D007438:Introns / Q000235:genetics; D007492:Iran; D008562:Membrane Glycoproteins / Q000235:genetics*; D054353:Perforin; D020641:Polymorphism, Single Nucleotide; D052899:Pore Forming Cytotoxic Proteins; D017422:Sequence Analysis, DNA
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin