Influence of the Toll-like receptor 9 1635A/G polymorphism on the CD4 count, HIV viral load, and clinical progression

Objective: To analyze the influence of single-nucleotide polymorphism (SNPs) in TLR2 (1892A/C and 2258G/A), TLR4 (896A/G and 1196C/T), and TLR9 (1635A/G) genes on CD4 count, HIV viral load, and clinical progression in a cohort of naive HIV-infected patients. Methods: TLR2, TLR4, and TLR9 SNPs were analyzed in 369 naive HIV-infected patients by real-time polymerase chain reaction and melting curve technology. TLR2 1892C/A and TLR9 1635A/G SNPs were also analyzed in a non-HIV-infected Population. Multivariate Multiple repression analysis and Cox regression analyses were performed to assess the potential association between the SNPs and the end points. Results: TLR2 and TLR4 SNPs were not associated with the end points of the Study. Regarding TLR9 1635A/G SNP, patients with the AA genotype showed statistically lower CD4 count (P = 0.003) and higher HIV viral load (P = 0.0018) compared with AG+GG genotypes at cohort entry. The multivariate analysis showed a significant association between the 1635AA genotype and both end points. Cox regression analysis showed that HIV clinical progression to clinical stage C and death due to AIDS-related events under anti-retroviral therapy was earlier in patients with the 1635AA genotype (P = 0.035, P = 0.017, respectively). Conclusions: TLR9 1635A/G SNP might have a role in HIV clinical disease progression.