Toll-like receptor 9 polymorphisms influence mother-to-child transmission of human immunodeficiency virus type 1.
BACKGROUND
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and play a crucial role in the host's innate immune response. Genetic variations in TLR genes may influence host-viral interactions and might impact upon the risk of mother-to-child transmission (MTCT) of Human Immunodeficiency Virus type 1 (HIV-1). The aim of this study was to investigate the influence of genetic variants of TLR 9 gene on MTCT.


METHODS
Three hundred children (118 HIV-1-infected and 182 HIV-1-uninfected) born to HIV-1-infected mothers were studied. Single nucleotide polymorphisms (SNPs) NM_017442.2: c.4-44G > A (rs352139) and c.1635A > G (rs352140) of the TLR9 gene were genotyped by TaqMan allelic discrimination assay. Statistical analyses were performed using SNPStats program.


RESULTS
When considered separately, neither of the two SNPs was significantly associated with risk of HIV-1 infection. However, the [A;A] and [G;G] haplotypes were associated with a higher risk of HIV-1 infection compared to the prevalent [G;A] haplotype [odds ratio (OR) = 3.16, 95% confidence interval (CI) 1.24-8.03, p = 0.016, and OR = 5.54, 95% CI 1.76-17.50, p = 0.004, respectively].


CONCLUSIONS
Overall, results demonstrate a significant correlation between specific genetic variants of the TLR9 gene and risk of MTCT of HIV-1, thus confirming a critical role of innate immunity in perinatal HIV-1 infection. Strategies aimed at modulating innate immunity might be useful for future treatment of pediatric HIV-1 infection and AIDS.
Ricci
Elisabetta
E
Department of Oncology and Surgical Sciences, Oncology Section, AIDS Reference Center, University of Padova, Via Gattamelata 64, 35128 Padova, Italy.
Malacrida
Sandro
S
Zanchetta
Marisa
M
Mosconi
Ilaria
I
Montagna
Marco
M
Giaquinto
Carlo
C
De Rossi
Anita
A
D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics* / Q000635:transmission*; D015497:HIV-1 / Q000502:physiology*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9