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Session 110 Poster Abstracts
Risk, Timing and Viral Genetics of Mother-to-Child Transmission
Session Day and Time: Wednesday, 1-4 pm
Room: Hall A


659
Role of Beta-Defensin-1 in Mother-to-Child HIV-1 Transmission
E Ricci1,2, S Malacrida1, M Zanchetta2,3, M Montagna3, C Giaquinto4, and Anita De Rossi*1,2,3
1Univ of Padova, Italy; 2AIDS Reference Ctr, Univ of Padova, Italy; 3IOV-IRCCS, Padova, Italy; and 4Univ of Padova, Italy

Background:  In mother-to-child transmission (MTCT) of HIV-1, the main source of pediatric AIDS, host-HIV-1 interaction occurs when the host's immune system is still under development. Defensins are small cationic antimicrobial peptides that play an important role in host defense, as part of the innate immune system. The aim of this study was to investigate the influence of 2 nucleotide polymorphisms (SNP) in the 5'-untranslated region (UTR) of the b-defensin-1 (DEFB1) gene on the MTCT of HIV-1.

Methods:  We analyzed 300 children, 118 HIV-1 infected and 182 HIV-1 uninfected. All children were born to HIV-1+ mothers who had not undergone any ART during pregnancy to prevent vertical transmission. Genomic DNA, extracted from peripheral blood mononuclear cells (PBMC), was evaluated for –44 C/G and –52 G/A polymorphisms by the TaqMan allelic discrimination assay. Genotypes were confirmed in randomly selected samples by sequence analysis. Hardy-Weinberg equilibrium tests, linkage disequilibrium estimation, haplotype frequencies and association of genotype with HIV infection status were evaluated using SNPStats and Haploview programs.

Results: Genotype distributions of the 2 polymorphisms were significantly different between the HIV-1-infected and uninfected children (p ≤0.05). The children with –52 GG genotype were at lower risk of HIV-1 infection than children with –52AA genotype (odd ratio [OR] 0.47, 95% CI 0.24 to 0.92, p = 0.03). The analysis of the –44 C/G polymorphism indicated that the –44 GG genotype tended to be associated with a lower risk of HIV-1 infection than the –44 CC genotype (OR 0.15, 95%CI 0.02 to 1.18, p = 0.07). Moreover, the haplotype –44G/–52G showed a significant protective role against HIV-1 infection compared to the haplotype –44C/–52A (OR 0.49, 95%CI 0.30 to 0.79, p = 0.007).

Conclusions:  Our results demonstrate a significant correlation between the 2 SNP located in the 5' UTR of the DEFB1 gene and risk of HIV-1-infection in a paediatric population confirming the importance of innate immunity in HIV-1 infection.