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

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.