Novel genetic association of TNF-α-238 and PDCD1-7209 polymorphisms with long-term non-progressive HIV-1 infection

• Published in: International journal of infectious diseases 2013-10, Vol.17 (10), p.e845-e850
• Main Authors: Nasi, Milena, Riva, Agostino, Borghi, Vanni, D’Amico, Roberto, Del Giovane, Cinzia, Casoli, Claudio, Galli, Massimo, Vicenzi, Elisa, Gibellini, Lara, De Biasi, Sara, Clerici, Mario, Mussini, Cristina, Cossarizza, Andrea, Pinti, Marcello
• Format: Article
• Language: English
• Subjects: Adaptive Immunity - genetics; Adult; Aged; Disease Progression; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; HIV; HIV Infections - genetics; HIV Infections - immunology; HIV-1 - immunology; Host genetics; Host-Pathogen Interactions - genetics; Humans; Infectious Disease; Long-term non-progressors; Major Histocompatibility Complex; Male; Middle Aged; Polymorphism; Polymorphism, Single Nucleotide; Programmed Cell Death 1 Receptor - genetics; Pulmonary/Respiratory; RNA, Untranslated; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2013.01.003

Summary Objectives About 2–5% of HIV-1-infected subjects, defined as long-term non-progressors (LTNPs), remain immunologically stable for a long time without treatment. The factors governing this condition are known only in part, and include genetic factors. Thus, we studied 20 polymorphisms of 15 genes encoding proinflammatory and immunoregulatory cytokines, chemokines and their receptors, genes involved in apoptosis, and the gene HCP5. Methods We analyzed 47 Caucasian LTNPs infected for >9 years, compared with 131 HIV-1-infected Caucasian patients defined as ‘usual progressors’. The genotypes were determined by methods based upon PCR, and the statistical analysis was performed by univariate logistic regression. Results The well-known CCR5Δ32 del32 allele, the cell death-related TNF-α-238 A and PDCD1-7209 T alleles, and HCP5 rs2395029 G, a non-coding protein associated with the HLA-B*5701, were found positively associated with the LTNP condition. No association was observed for other single nucleotide polymorphisms (SDF-1-801, IL-10-592, MCP-1-2518, CX3CR1 V249I, CCR2V64I, RANTES-403, IL-2-330, IL-1β-511, IL-4-590, FASL IVS3nt-169, FAS-670, FAS-1377, FASL IVS2nt-124, PDCD1-7146, MMP-7-181, and MMP7-153). Conclusions The novel genetic associations between allelic variants of genes TNF-α-238 and PDCD1-7209 with the LTNP condition underline the importance of host genetic factors in the progression of HIV-1 infection and in immunological preservation.