ABSTRACT: 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.
