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

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 <i>DDAH 1</i> (<i>rs669173</i>, <i>rs7521189</i>) and <i>DDAH 2</i> gene polymorphisms (<i>rs805305</i>, <i>rs3131383</i>) 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 (<i>rs669173</i>, <i>rs7521189</i>, <i>rs805305</i>, and <i>rs3131383</i>) 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 <i>rs669173</i> and <i>rs7521189</i> SNPs of the <i>DDAH 1</i> gene and <i>rs3131383</i> of the <i>DDAH 2</i> 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 <i>rs805305</i> variant of the <i>DDAH 2</i> 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.

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Journal
International Journal of Molecular Sciences
Published
2025-04-01
DOI
https://doi.org/10.3390/ijms26073271
Primary Topic
Pregnancy and preeclampsia studies
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article
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article

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

Zinhle Pretty Mlambo, Nompumelelo P. Mkhwanazi, Mbuso Herald Mthembu, Thajasvarie Naicker et al.
International Journal of Molecular Sciences
Pregnancy and preeclampsia studies
article

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

Zinhle Pretty Mlambo, Nompumelelo P. Mkhwanazi, Mbuso Herald Mthembu, Thajasvarie Naicker, Samukelisiwe Sibiya
article en

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 <i>DDAH 1</i> (<i>rs669173</i>, <i>rs7521189</i>) and <i>DDAH 2</i> gene polymorphisms (<i>rs805305</i>, <i>rs3131383</i>) 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 (<i>rs669173</i>, <i>rs7521189</i>, <i>rs805305</i>, and <i>rs3131383</i>) 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 <i>rs669173</i> and <i>rs7521189</i> SNPs of the <i>DDAH 1</i> gene and <i>rs3131383</i> of the <i>DDAH 2</i> 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 <i>rs805305</i> variant of the <i>DDAH 2</i> 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.

International Journal of Molecular SciencesVol. 26(7)
University of KwaZulu-Natal (ZA)
Gender equality
Openalex Percentile: Top 91%
Pregnancy and preeclampsia studies
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