Asymmetric Dimethylaminohydrolase Gene Polymorphisms Associated with Preeclampsia Comorbid with HIV Infection in Pregnant Women of African Ancestry

Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor associated with vascular disease, which is prevalent in human plasma. Two isoforms of the enzyme dimethylarginine dimethylaminohydrolase (DDAH), DDAH 1 and 2, degrade ADMA. This study investigates the association of DDAH 1 (rs669173, rs7521189) and DDAH 2 gene polymorphisms (rs805305, rs3131383) with the risk of preeclampsia (PE) comorbidity with human immunodeficiency virus (HIV) infection in pregnant women of African ancestry. A total of 405 women were enrolled in this study: 204 were PE, 201 were normotensive pregnant, and 202 were HIV positive. DNA was extracted from whole blood, and SNPs (rs669173, rs7521189, rs805305, and rs3131383) were amplified to detect single-nucleotide polymorphisms (SNPs). After PCR amplification, allelic discrimination was examined. Comparisons were conducted utilizing the Chi-squared test. Our findings indicated that preeclamptic women displayed a greater prevalence of the three variants compared to those with both PE and HIV infection. There is an association between the rs669173 and rs7521189 SNPs of the DDAH 1 gene and rs3131383 of the DDAH 2 gene, which could play a role in reducing the bioavailability of nitric oxide (NO), which affects endothelial function, leading to the development of PE in pregnant women of African ancestry. In contrast, the rs805305 variant of the DDAH 2 gene was not significantly associated with PE development. Interestingly, none of the SNPs investigated correlated with HIV infection or could be attributed to the human allelic variant influence on HIV infection outcome.