HLA-G DNA sequence variants and risk of perinatal HIV-I transmission

Abstract

Background: HLA-G gene is a non-classical MHC class I molecule that is highly expressed in the trophoblast at the maternal-fetal interface. In an attempt to elucidate possible immunological mechanisms facilitating protection of infants born to human immunodeficiency virus type (HIV-I) infected mothers, we have been studying genetic variations in the coding and untranslated regions of HLA-G antigen between HIV-I-infected mothers and their infected or uninfected infants. This study investigated whether HLA-G DNA sequence variants are associated with perinatal HIV-I transmission. Results: Genomic DNA samples were obtained from a nested case-control study of 34 mother-child pairs co-enrolled in a cohort of the Perinatal AIDS Collaborative Transmission Study in New York. The samples were from two groups predominantly of African-American and Hispanic origin: In the first group, both mother and child were HIV-I-infected; in the second group, only the mother was infected while the child remained uninfected. Genotyping of HLA-G gene were performed on the extracted DNA from peripheral blood mononuclear cells using PCR based sequencing and restriction fragment-length polymorphism analyses. Among the studied HLA-G exons, dissimilarities in HLA-G DNA sequence variants between the HIV-I non-transmitting mother child pairs were mostly observed in exon 8-3′-untranslated region at nucleotide positions T3742A, C3743T, G3777C (P = 0.001). Non-transmitting HIV-I mother child pairs exhibited dissimilarities at nucleotide position C3743T allele with decreased risk of perinatal HIV-I transmission, compared with HIV-I transmitting mother-child pairs carrying this allele (odds ratio 0.02 [95% confidence interval 0.00-0.15] P = 0.00001). In addition, heterozygous dissimilarities at nucleotide positions C634G and 714 insT/G in the 5′-upstream regulatory region were observed between the mother child pairs of the HIV-I-non-transmitting group while homozygous similarities of C634C, and either 714insG/G or mother-child pairs with similar 714insT/G were observed among the transmitting group in the same region. Conclusion: This study identified new variants in the HLA-G gene and provides further evidence that dissimilarities in the HLA-G DNA sequence variants could influence the transmission of HIV-I from infected mothers to their infants. © 2006 Aikhionbare et al; licensee BioMed Central Ltd.