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

Abstract

BackgroundSouth 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.MethodsThis 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.ResultsThere 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).ConclusionsOur 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.

Association of miR-146 rs2910164, miR-196a rs11614913, miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn’s disease

“…Genomic DNA from whole peripheral blood containing EDTA was extracted using validated techniques (NucleoSpin Blood kit; Macherey-Nagel, Germany). PCR–RFLP was used to determine the rs2910164 and rs11614913 was performed using T-ARMS-PCR assay as described previously genotypes as previously described[ 38 , 39 ]. Regarding the rs113054794 we used PCR-RFLP method.…”

MicroRNA-Related Polymorphisms in Infectious Diseases—Tiny Changes With a Huge Impact on Viral Infections and Potential Clinical Applications

“…The association between miR-27a rs895819 and BMI described by Maharaj et al ( 112 ) is quite interesting and deserves to be replicated in other populations with different genetic backgrounds. Posteriorly, the same group described a potential impact of miR-146a C/G SNP (rs2910164) on HIV-positive South African women with preeclampsia ( 115 ). Specifically, GC/CC genotypes were associated with a reduced susceptibility to severe preeclampsia in HIV-positive pregnant women on HAART (Highly Active Antiretroviral Therapy).…”

“…Specifically, GC/CC genotypes were associated with a reduced susceptibility to severe preeclampsia in HIV-positive pregnant women on HAART (Highly Active Antiretroviral Therapy). In addition, the miR-146a rs2910164 seems to have an influence on IL-2 levels of pregnant women ( 115 ). These results suggest an influence on the progression of HIV-related diseases.…”

“…These results suggest an influence on the progression of HIV-related diseases. However, the patients studied by Maharaj et al ( 112 , 115 ) represent a very particular group of women, and before assuming that miR-27a rs895819 or miR-146a rs2910164 have an important influence on the clinical status of HIV-infected individuals from different genetic backgrounds, these SNPs must be studied in distinct populations (infected and non-infected by HIV) in studies recruiting men and women with different health status.…”

Maternal miRNA-146a G/C rs2910164 variation, HIV/AIDS and nitrogen oxide pollution exposure collectively affects foetal growth

“…32,33 The rs2910164 was associated with severe preeclampsia in HIV+ Black South African women on highly active antiretroviral therapy (HAART). 34 To date, studies investigating the role of rs2910164 in ABO are scarce.…”