HLA-G Polymorphisms Associated with HIV Infection and Preeclampsia in South Africans of African Ancestry

OBJECTIVES: HLA-G, part of the major histocompatibility complex (MHC), is associated with the risk of developing preeclampsia (PE). In this study, we determined the contribution of specific HLA-G polymorphisms on the risk of developing preeclampsia in HIV-infected and uninfected South Africans of African ancestry. METHODS: One hundred and ninety-three women of African ancestry were enrolled (74 HIV-uninfected normotensive, 60 HIV-infected normotensive, 34 HIV-uninfected, and 25 HIV-infected preeclamptics). Sanger sequencing of the untranslated region was performed to genotype six SNPs, i.e., 14 bp Ins/Del of rs66554220, rs1710, rs1063320, rs1610696, rs9380142, and rs1707). RESULTS: For rs66554220, we have the following results: (a) based on pregnancy type—the Ins/Ins and Del/Ins genotype frequency was higher in preeclampsia (PE) compared to normotensive pregnancies (Ins/Ins vs. Del/Ins, P = 0.02(∗): OR (95%CI) = 13.44 (0.7222–249.9); Del/Del vs. Del/Ins, P = 0.03(∗): OR (95%CI) = 2.95 (1.10–7.920)); (b) based on HIV status—the Ins/Ins showed both genotypic and allelic association with HIV infection. HIV-infected PE has higher Ins/Ins genotypic and allelic frequencies compared to HIV-uninfected PE (Ins/Ins vs. Del/Ins, P = 0.005(∗∗): OR (95%CI) = 21.32 (1.71–4.17); Ins, P = 0.005(∗∗); OR (95%IC) = 21.32 (1.71–4.17)). For rs1707, we have the following results: (a) based on pregnancy type—there were CT genotypic frequencies in PE, more especially LOPE compared to normotensive pregnancies (TT vs. CT, P = 0.0092(∗∗): OR (95%CI) = 5.(1.39 − 25.64)), and no allelic association was noted; (b) based on HIV status—CT was higher in HIV-infected LOPE compared to uninfected LOPE (TT vs. TC, P = 0.0006(∗∗∗): OR (95%CI) = 40.00 (2.89 − 555.1)). For rs1710 and rs1063320, no significant differences in the genotype and allele frequencies were noted based on pregnancy type and HIV status. For rs9380142, we have the following results: (a) based on pregnancy type—no significant differences were noted between normotensive compared to PE pregnancies; (b) based on HIV status—AA genotypes occurred more in the HIV-infected PE group (AA vs. GG, P = 0.02(∗): OR (95%CI) = 13.97 (0.73 − 269.4)), while A allelic frequency occurred more in HIV-infected PE, especially LOPE compared to uninfected groups (A vs. G, P = 0.0003(∗∗∗): OR (95%CI) = 10.72 (2.380 − 48.32); P = 0.02(∗): OR (95%CI) = 9.00 (1.07 − 75.74)). For rs1610696, we have the following results: (a) based on pregnancy type—genotypic and allelic frequencies of CC were higher in PE compared to normotensive pregnancies (CC vs. GG, P = 0.0003(∗∗∗): OR (95%CI) = 31.87 (1.861 − 545.9); C, P = 0.0001(∗∗∗): OR (95%IC) = 21.91 (2.84 − 169.0)); (b) based on HIV status—GG frequencies were higher in the HIV-infected PE more especially LOPE groups (GG vs. GC, P = 0.02(∗): OR (95%CI) = 16.87 (0.81 − 352.1); GG vs. CC, P = 0.0001(∗∗∗): OR (95%CI) = 159.5 (13.10 − 1942)). CONCLUSION: Selected HLA-G 14 bp polymorphisms (Ins/Ins) and genotypic and allelic differences in rs9380142, rs1610696, and rs1707 are associated with the pathogenesis of preeclampsia in HIV-infected South African women of African ancestry. More genetic studies evaluating the association between preeclampsia and HIV infection are needed to improve diagnosis and antenatal care.