Journal Article

Association of Toll-Like Receptor 4 Asp299Gly and Thr399Ile Polymorphisms with Increased Infection Risk in Patients with Advanced HIV-1 Infection

Antonios I. Papadopoulos, Bart Ferwerda, Anastasia Antoniadou, Vissaria Sakka, Lambrini Galani, Dimitra Kavatha, Periklis Panagopoulos, Garyphalia Poulakou, Kyriaki Kanellakopoulou, Jos W. M. van der Meer, Evangelos J. Giamarellos-Bourboulis and Mihai G. Netea

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 2, pages 242-247
Published in print July 2010 | ISSN: 1058-4838
Published online July 2010 | e-ISSN: 1537-6591 | DOI: https://dx.doi.org/10.1086/653607
Association of Toll-Like Receptor 4 Asp299Gly and Thr399Ile Polymorphisms with Increased Infection Risk in Patients with Advanced HIV-1 Infection

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Background. The Toll-like receptor 4 (TLR4) is an essential component of the innate immune response to various microorganisms. We investigated the association between TLR4 polymorphism and the risk of acquiring severe infections, in patients with human immunodeficiency virus (HIV)-1 infection.

Methods. The presence of TLR4 Asp299Gly and Thr399Ile single nucleotide polymorphisms (SNPs) was determined in a cohort of 199 HIV-1 infected patients and evaluated in relation to the occurrence of various infections.

Results. One hundred seventy-two patients were homozygous for the wild-type genotype; 22 patients (11%) were heterozygous for both SNPs; 4 were heterozygous for 1 polymorphism; 1 patient was heterozygous for the Asp299Gly SNP and homozygous for the Thr399Ile SNP. Of individuals with a nadir CD4 cell count of <100 cells/mm3, those who carried both SNPs, compared with those who carried the wild-type genotype, demonstrated a >3-fold increase in the odds ratio (OR) of any serious infection (OR, 6.33 vs OR, 1.83, P=.043).

Conclusions. This study suggests an association between the presence of TLR4 Asp299Gly and Thr399Ile polymorphisms and the occurrence of serious infections in HIV-1 infected patients with a history of nadir CD4 cell count of <100 cells/mm3.

Journal Article.  3275 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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