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.
Highlights
Preeclampsia (PE) is a human-specific multisystemic disorder affecting 3–17% of pregnancies worldwide [1]
The main findings of this study indicate that in preeclampsia, human leukocyte antigen (HLA-G) 14 bp polymorphism (Ins/Ins and Del/Ins) and genotypic and allelic differences in rs9380142, rs1610696, and rs1707 are associated with human immune deficiency virus (HIV) infection and preeclampsia in South African women of African ancestry
This study has shown that HIV infection may be associated with selected HLA-G gene polymorphisms and the risk of preeclampsia in HIV-infected South Africans of African ancestry
Summary
Preeclampsia (PE) is a human-specific multisystemic disorder affecting 3–17% of pregnancies worldwide [1]. The diagnosis of PE is made clinically in the presence of new-onset hypertension (systolic and diastolic blood pressure of ≥140/90 mmHg) and proteinuria (≥300 mg in a 24-hour urine collection) after the 20th week of pregnancy [1, 2]. The exact aetiology is unknown [4], it is thought to develop as a result of placental maladaptation due to impaired uterine spiral artery remodelling [5]. The spiral arterioles are transformed into widebore channels that enable adequate blood supply to the developing foetus. In PE, the trophoblast invasion is deficient with a lack of physiological transformation of myometrial spiral arteries. The actual reason for the poor cytotrophoblast invasion remains unknown, both genetic and immune responses are thought to play a role [6]
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