The TLR4 ASP299GLY polymorphism is a risk factor for active tuberculosis in Caucasian HIV-infected patients.

Abstract:

INTRODUCTION: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. OBJECTIVES: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.

journal_name

Curr HIV Res

journal_title

Current HIV research

authors

Pulido I,Leal M,Genebat M,Pacheco YM,Sáez ME,Soriano-Sarabia N

doi

10.2174/157016210791111052

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

253-8

issue

3

eissn

1570-162X

issn

1873-4251

pii

ABS-66a

journal_volume

8

pub_type

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