Association of the eNOS Gene Intron 4 VNTR Polymorphism with Susceptibility to Preeclampsia and Its Severity in an Algerian Cohort

Background/Objectives: Preeclampsia (PE) is the primary cause of maternal and perinatal morbidity and mortality on a global scale. It is driven by a multifactorial aetiology, in which genetic factors involved in blood pressure regulation, including the endothelial nitric oxide synthase (eNOS) gene, play an important role. This study aimed to investigate the association between eNOS gene polymorphisms and the development and severity of PE in an Algerian cohort. Methods: A total of 305 Algerian women, comprising 124 patients with PE and 181 healthy controls, were genotyped for two polymorphisms: intron 4 variable number tandem repeat (VNTR) (4a/4b) and the −786 T>C promoter variant. Genotyping was performed using standard polymerase chain reaction (PCR) for VNTR and polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) for the −786 T>C variant. Results: Our results revealed no significant difference in the allelic or genotypic frequencies of the −786 T>C polymorphism between the cases and controls (p > 0.05). Interestingly, the frequency of the protective “4b” allele was significantly lower in cases than in controls (odds ratio (OR) = 0.400 [0.278–0.575]; p <0.0001). However, the “4a” allele and the 4a/4a genotype were significantly associated with an increased risk of preeclampsia (OR = 2.50 [1.74–3.59], p < 0.0001; and OR = 6.20 [2.85-13.50], p < 0.0001, respectively). Furthermore, they were correlated with disease severity (allelic: OR = 2.76 [1.60–4.75], p = 0.0002; and genotypic: OR = 4.64 [1.83-11.78], p = 0.0003). Conclusions: These findings support the potential role of the eNOS VNTR 4a/4b polymorphism in both the risk and severity of preeclampsia in the Algerian population.