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.

Perspective of HLA-G Induced Immunosuppression in SARS-CoV-2 Infection

“…Association between HLA-G polymorphism and viral infection has been documented in a number of studies. HLA-G *01:01:08 was reported to be a risk factor for HIV-1 infection in Zimbabwean while 3’UTR 14-bp In/14-bp In was a risk factor for HIV infection in South Africans of African ancestry women ( 70 , 71 ). 14-bp del/14-bp del and HLA-G*01:04:01 /14-bp del genotypes, and UTR-2 and UTR-3 haplotypes were found to be the risk factors for hepatitis C virus ( 72 , 73 ).…”

KIR2DL4/HLA‐G polymorphisms were associated with HCV infection susceptibility among Chinese high‐risk population

“…We found the relationship between the heterozygosity at HLA‐G rs9380142 (chromosome position: 29798794) and an increased risk of HCV susceptibility. In the previous studies, HLA‐G rs9380142 was reported to be associated with the preeclampsia in HIV‐infected women, arthritis hip arthritis and deformity in enthesitis‐related arthritis‐juvenile idiopathic arthritis 28,29 . HLA‐G Rs9380142 maps to the 3′UTR region.…”

Association of parental HLA-G polymorphisms with soluble HLA-G expressions and their roles on recurrent implantation failure: A systematic review and meta-analysis

“…Further studies are needed to confirm whether an association exists between HLA-G 14bp ins/del polymorphism with RIF in patients of other ethnicities. In addition to RIF, maternal HLA-G 14bp ins/del polymorphism is also reported to be associated with preeclampsia ( 95 ), gestational diabetes mellitus ( 96 ), and recurrent miscarriage ( 97 – 99 ). Almeida et al.…”