HLA‐G Polymorphisms Associated with HIV Infection and Preeclampsia in South Africans of African Ancestry
Authors: Phoswa Wendy N. , Ramsuran Veron , Naicker Thajasvarie , Singh Ravesh , Moodley Jagidesa 
Published: June 2020

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.