A deliberative public engagement study on heritable human genome editing among South Africans: Study results.

This paper reports the results of a public engagement study on heritable human genome editing (HHGE) carried out in South Africa, which was conducted in accordance with a study protocol that was published in this journal in 2021. This study is novel as it is the first public engagement study on HHGE in Africa. It used a deliberative public engagement (DPE) methodology, entailing inter alia that measures were put in place to ensure that potential participants became informed about HHGE, and that deliberations between the participants were facilitated with the aim of seeking consensus. A diverse group of 30 persons was selected to participate in the DPE study, which took place via Zoom over three consecutive weekday evenings. The main results are: Provided that HHGE is safe and effective, an overwhelming majority of participants supported allowing the use of HHGE to prevent genetic health conditions and for immunity against TB and HIV/Aids, while significant majorities opposed allowing HHGE for enhancement. The dominant paradigm during the deliberations was balancing health benefits (and associated improvements in quality of life) with unforeseen health risks (such as loss of natural immunity). The seriousness of a health condition emerged as the determining factor for the policy choice of whether to allow an application of HHGE. More generally, equal access to HHGE qua healthcare service featured as an important value, and it was uncontested that the South African government should allocate resources to promote scientific research into HHGE. These results are aligned with the policy principles for regulating HHGE in South Africa suggested by Thaldar et al. They call for urgent revision of South African ethics guidelines that currently prohibit research on HHGE, and for dedicated HHGE legal regulations that provide a clear and comprehensive legal pathway for researchers who intend to conduct HHGE research and clinical trials.

A virtual deliberative public engagement study on heritable genome editing among South Africans: Study protocol.

This article outlines the protocol for a prospective study for virtual deliberative public engagement on heritable genome editing in humans. The study intends to create a platform for a diverse group of 25-30 South Africans to engage with a facilitator and each other on 15 policy questions regarding heritable genome editing, with a focus on: a) the prevention of heritable genetic conditions; b) editing for immunity; and c) editing for enhancement. The aim is to understand the views on these issues so as to inform further research and policy, and to analyse the process and effect of deliberation on opinion. Participants will be expected to study the provided resource materials and pass the entrance exam-aligning with the protocols of the Harvard Personal Genome Project. In this way, the commitment, openness and basic knowledge of the candidates will be tested to ascertain whether they are suitable participants for the deliberative engagement.

MicroRNA-146a rs2910164 is associated with severe preeclampsia in Black South African women on HAART.

BACKGROUND: South African (SA) Black women have a high prevalence of preeclampsia and HIV, both conditions associated with increased inflammation. miR-146a is an inflammatory-associated miR and a common single nucleotide polymorphism (rs2910164) has been associated with several disease conditions. To date, this SNP has not been investigated in SA Black women. We therefore aimed to investigate the miR-146a G > C SNP in SA Blacks with preeclampsia, and further examine possible association among preeclamptic (PE) women with HIV infection on HAART. METHODS: This hospital-based, case-control study included 95 normotensive and 98 PE Black SA women (aged 16-46 years old). Patients and controls were genotyped by PCR-RFLP. Using a Cytometric Bead Array assay, serum cytokine levels (including Th1- and Th2-related cytokines) were determined in 4 groups of pregnant women, viz: normotensive, HIV infected, PE + HIV infected, and PE women. RESULTS: There was no significant association between the miR-146a polymorphism and PE susceptibility in our data. However, in the subgroup analyses, the variant genotypes (GC/CC) were significantly associated with lower severe PE risk (p = 0.0497), more especially in the presence of HIV and HAART (p = 0.017). In the normotensive group, the variant genotypes were associated with lower IL-2 in both the total normotensive group (269 ± 1.26 (36) vs 273 ± 1.31 (23); p = 0.035) and the PE HIV+ sub-group 265 ± 1.54 (19) vs 271 ± 1.38 (11); p = 0.008). CONCLUSIONS: Our study suggests that miR-146a rs2910164 polymorphism might not be associated with PE susceptibility, cytokines or related features. However, the miR-146a GC/CC genotype might reduce susceptibility to severe PE, which might be further influenced by the presence of co-morbid HIV infection among pregnant women on HAART. This variant genotype may also be associated with reduced circulating IL-2 levels and thus reduced pro-inflammatory response in normotensive women, which may be further influenced by the presence of HIV infection and HAART.

microRNA-27a rs895819 is associated with obesity in HIV infected preeclamptic Black South African women on HAART.

BACKGROUND: Preeclampsia (PE) and HIV/AIDS present a major health challenge globally. South Africa has the highest disease burden of both HIV/AIDS and PE in the world. Despite extensive research, the pathophysiology of these conditions is not completely understood, however a genetic predisposition in women may affect susceptibility. MiRNA-27a regulates adipogenesis and glucose metabolism. A single nucleotide polymorphism (SNP) in miRNA-27a (rs895819T > C) has shown to have disparate effects in various populations. This study investigated the frequency of rs895819 in pregnant normotensive and preeclamptic Black South African (SA) women. METHODS: Enrollment into the study included: normotensive (n = 95; 45 HIV+; 80 analysed for rs895819T > C, age range: 16-46 years) and PE patients (n = 98; 45 HIV+; 56 analysed for rs895819T > C), age range: 16-42 years). DNA was isolated from peripheral blood mononuclear cells (PBMC). Genotyping of miRNA-27a rs895819 was detected using a TaqMan® SNP Genotyping assay. RESULTS: We did not find a significant association of miR-27a polymorphism with PE susceptibility in our data. However, in the subgroup analysis (based in HIV status), the variant genotypes (TC/CC) were associated with higher body mass index (BMI) among PE women (32.57 vs. 29.25, p = 0.064), significantly in the presence of HIV infection (33.47 vs. 27.8, p = 0.005). CONCLUSION: The results of this study suggests that miR-27a rs895819 may not be associated with PE susceptibility; however, the miR-27a TC/CC genotype increases susceptibility to elevated BMI in PE, which may be significantly influenced by co-morbid HIV infection among pregnant women on HAART.