Mthembu Mbuso Herald, Sibiya Samukelisiwe, Mlambo Zinhle Pretty, Mkhwanazi Nompumelelo P, Naicker Thajasvarie
Department of Obstetrics and Gynaecology, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4041, South Africa.
Optics and Imaging Centre, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa.
Int J Mol Sci. 2025 Apr 1;26(7):3271. doi: 10.3390/ijms26073271.
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 (, ) and gene polymorphisms (, ) 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 (, , , and ) 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 and SNPs of the gene and of the 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 variant of the 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.
不对称二甲基精氨酸（ADMA）是一种与血管疾病相关的内源性一氧化氮合酶（NOS）抑制剂，在人体血浆中普遍存在。二甲基精氨酸二甲胺水解酶（DDAH）有两种同工型，即DDAH 1和DDAH 2，可降解ADMA。本研究调查了非洲裔孕妇中DDAH 1和DDAH 2基因多态性（rs1611115、rs743572）与先兆子痫（PE）合并人类免疫缺陷病毒（HIV）感染风险的关联。本研究共纳入405名女性：204名患有PE，201名血压正常的孕妇，202名HIV阳性。从全血中提取DNA，并扩增单核苷酸多态性（SNP，rs1611115、rs743572、rs2070744和rs2297518）以检测单核苷酸多态性。PCR扩增后，进行等位基因鉴别。采用卡方检验进行比较。我们的研究结果表明，与同时患有PE和HIV感染的女性相比，先兆子痫女性中这三种变体的患病率更高。DDAH 1基因的rs1611115和rs743572 SNP与DDAH 2基因的rs2297518之间存在关联，这可能在降低一氧化氮（NO）的生物利用度方面发挥作用，而NO会影响内皮功能，导致非洲裔孕妇发生PE。相比之下，DDAH 2基因的rs2297518变体与PE的发生没有显著关联。有趣的是，所研究SNP均与HIV感染无关，也不能归因于人类等位基因变体对HIV感染结果的影响。
