Association of toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms with increased infection risk in patients with advanced HIV-1 infection.
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/mm(3), 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/mm(3).
Papadopoulos
Antonios I
AI
4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece. antpapa1@otenet.gr
Ferwerda
Bart
B
Antoniadou
Anastasia
A
Sakka
Vissaria
V
Galani
Lambrini
L
Kavatha
Dimitra
D
Panagopoulos
Periklis
P
Poulakou
Garyphalia
G
Kanellakopoulou
Kyriaki
K
van der Meer
Jos W M
JW
Giamarellos-Bourboulis
Evangelos J
EJ
Netea
Mihai G
MG
D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology* / Q000235:genetics*; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D017422:Sequence Analysis, DNA; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D051197:Toll-Like Receptor 4