Maternal human leukocyte antigen-G (HLA-G) genetic variants associate with in utero mother-to-child transmission of HIV-1 in Black South Africans

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.