title: Maternal human leukocyte antigen-G (HLA-G) genetic variants associate with in utero mother-to-child transmission of HIV-1 in Black South Africans.
abstract: A 14-bp insertion/deletion (indel) within the 3' untranslated region (3'UTR) that affects HLA-G expression has been associated with HIV-1 mother-to-child transmission (MTCT). However, other 3'UTR single nucleotide polymorphisms (SNPs) that influence HLA-G mRNA stability have been described but not analysed in the context of MTCT, and little is known about the role of HLA-G alleles. We examined HLA-G alleles and 3'UTR SNPs, including the 14-bp indel, in 216 mother-infant pairs from Johannesburg, South Africa. Mother-infant pairs were classified as HIV-1 non-transmitting (NT, n=144) or HIV-1 transmitting (TR, n=72) with either intrapartum (IP, n=29) or in utero (IU, n=19) infected infants. We found HLA-G allele, G(∗)01:01:02 (in strong linkage disequilibrium with the 14-bp insertion) and +3187G SNP were significantly over-represented in IU-TR mothers compared to NT mothers (P=0.036, OR=2.26; P=0.011, OR=2.96, respectively). These findings suggest that maternal HLA-G alleles and/or SNPs that might alter expression of HLA-G potentially influence IU HIV-1 MTCT.
authors.affiliation: Centre for HIV & STIs, National Institute for Communicable Diseases, National Health Laboratory Service, and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Hong
authors.affiliation: Centre for HIV & STIs, National Institute for Communicable Diseases, National Health Laboratory Service, and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Maria
authors.initials: M
authors.lastname: Paximadis
authors.affiliation: Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa, and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Glenda E
authors.initials: GE
authors.lastname: Gray
authors.affiliation: Gertrude H. Sergievsky Centre, College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
authors.affiliation: Centre for HIV & STIs, National Institute for Communicable Diseases, National Health Laboratory Service, and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: carolinet@nicd.ac.za.
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Tiemessen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D044383:Black People / Q000706:statistics & numerical data; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000453:epidemiology* / Q000235:genetics* / Q000635:transmission*; D015497:HIV-1; D059951:HLA-G Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D009035:Mothers; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013019:South Africa / Q000453:epidemiology; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens
keywords: HIV-1; HLA-G 3′UTR haplotypes; HLA-G alleles; Mother-to-child transmission (MTCT)