Journal of acquired immune deficiency syndromes (1999) · 2009
Role of beta-defensin-1 polymorphisms in mother-to-child transmission of HIV-1.
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Ricci Elisabetta, Malacrida Sandro, Zanchetta Marisa, Montagna Marco, Giaquinto Carlo, De Rossi Anita
Аннотация
BACKGROUND AND OBJECTIVES: Mother-to-child transmission (MTCT) of HIV-1, the main source of pediatric AIDS, is multifactorial. Defensins provide microbial barriers and function as effectors of innate immunity. This study investigated the relationship between genetic variants of beta-defensin-1 gene and MTCT of HIV-1.
PATIENTS AND METHODS: Three hundred children, 118 HIV-1 infected and 182 HIV-1 uninfected, born to HIV-1-infected mothers who had not undergone antiretroviral therapy during pregnancy, and 84 HIV-1-infected mothers were analyzed. The single nucleotide polymorphisms -44C/G (rs1800972) and -52G/A (rs1799946) were genotyped by TaqMan allelic discrimination assay and sequencing. Statistical analyses were performed using SNPStats and Bonferroni correction for multiple tests.
RESULTS: In children, the -52GG genotype and the -44G/-52G haplotype had a protective role against HIV-1 infection [odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.31 to 0.86, P = 0.03 and OR = 0.50, 95% CI 0.31 to 0.83, P = 0.014, respectively]. In mothers, the -52GG genotype and the -44G/-52G haplotype were associated with low levels of HIV-1 plasma viremia (<1000 copies/mL) and a lower risk of maternal HIV-1 transmission (OR = 0.14, 95% CI 0.03 to 0.67, P = 0.009 and OR = 0.23, 95% CI 0.08 to 0.66, P = 0.012, respectively).
CONCLUSIONS: These results demonstrate a significant relationship between genetic variants of beta-defensin-1 gene, viral load, and MTCT of HIV-1, thus supporting a critical role of innate immunity in pediatric HIV-1 infection.
PATIENTS AND METHODS: Three hundred children, 118 HIV-1 infected and 182 HIV-1 uninfected, born to HIV-1-infected mothers who had not undergone antiretroviral therapy during pregnancy, and 84 HIV-1-infected mothers were analyzed. The single nucleotide polymorphisms -44C/G (rs1800972) and -52G/A (rs1799946) were genotyped by TaqMan allelic discrimination assay and sequencing. Statistical analyses were performed using SNPStats and Bonferroni correction for multiple tests.
RESULTS: In children, the -52GG genotype and the -44G/-52G haplotype had a protective role against HIV-1 infection [odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.31 to 0.86, P = 0.03 and OR = 0.50, 95% CI 0.31 to 0.83, P = 0.014, respectively]. In mothers, the -52GG genotype and the -44G/-52G haplotype were associated with low levels of HIV-1 plasma viremia (<1000 copies/mL) and a lower risk of maternal HIV-1 transmission (OR = 0.14, 95% CI 0.03 to 0.67, P = 0.009 and OR = 0.23, 95% CI 0.08 to 0.66, P = 0.012, respectively).
CONCLUSIONS: These results demonstrate a significant relationship between genetic variants of beta-defensin-1 gene, viral load, and MTCT of HIV-1, thus supporting a critical role of innate immunity in pediatric HIV-1 infection.