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 polymorphisms (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 regression 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 antiretroviral 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.
Soriano-Sarabia
Natalia
N
Laboratory of Immunovirology, Seville Biomedicine Institute (IBIS), Service of Infectious Diseases, Virgen del Rocío Hospital, Seville, Spain.
Vallejo
Alejandro
A
Ramírez-Lorca
Reposo
R
Rodríguez
María del Mar
Mdel M
Salinas
Ana
A
Pulido
Ildefonso
I
Sáez
María E
ME
Leal
Manuel
M