The TLR4 ASP299GLY polymorphism is a risk factor for active tuberculosis in Caucasian HIV-infected patients.
BACKGROUND
Tuberculosis (TB) is a pandemic infectious disease especially frequent in HIV-infected patients. Toll-like receptor (TLR) 4 has been described to play a main role in the innate immunity against TB. In fact, single nucleotide polymorphisms (SNPs) in TLRs may influence AIDS disease progression. The association between two particular SNPs in human TLR4 (Asp299Gly and Thr399Ile) and active TB has been studied in non-HIV Africans with contradictory results. However, studies focusing on the effect of these TLR4 SNPs in active TB within a Caucasian HIV population are lacking.


OBJECTIVE
To analyze the association between TLR4 Asp299Gly and Thr399Ile SNPs and active TB, in Caucasian Mediterranean HIV-infected individuals.


METHODS
468 HIV-infected patients were analyzed. TLR4 genotyping was performed by real-time PCR and melting curve technology.


RESULTS
TB was diagnosed in 59 (12,6%) patients. In a bivariate analysis several variables resulted significantly associated with active TB; intravenous drugs use (OR= 2.2; 95% CI [1.2-3.8]), hepatitis C virus (HCV) co-infection (OR= 3.4; 95% CI [1.6-7.1]), CD4 count (p<0.001), HIV viral load (p=0.003), latent TB prophylaxis (OR= 0.3; 95% CI [0.1-0.5]), and TLR4 Asp299Gly (OR= 2.0; 95% CI [1.1-4.2]). No statistical association was found for the TLR4 Thr399Ile. After a multivariate analysis, HCV co-infection (OR= 3.8; 95% CI [2.2-6.5]), baseline CD4 count (OR= 0.996; 95% CI [0.994-0.998]), TLR4 Asp299Gly (OR= 2.57; 95% CI [1.18-5.61]) were independently associated with active TB and inversely with latent TB prophylaxis (OR= 0.24; 95% CI [0.01-0.60]).


CONCLUSIONS
We describe an independent association between TLR4 Asp299Gly SNP and active TB in Caucasian Mediterranean HIV-infected patients.
Immunovirology Laboratory, Seville Biomedicine Institute (IBIS), Infectious Disease Service, Virgen del Rocío University Hospital, Seville, Spain.
Ildefonso
I
Pulido
Manuel
M
Leal
Miguel
M
Genebat
Yolanda M
YM
Pacheco
María Eugenia
ME
Sáez
Natalia
N
Soriano-Sarabia
D000328:Adult; D019943:Amino Acid Substitution; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000150:complications* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology*; D044366:Transition Temperature; D014376:Tuberculosis / Q000208:ethnology* / Q000235:genetics* / Q000276:immunology; D044465:White People
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4