Association between endothelial nitric oxide synthase (eNOS) gene variants and nitric oxide production in preeclampsia: a case-control study in Ghana

Evidence suggests that a major cause of PE is endothelial dysfunction emanating from the reduced bioavailability of Nitric oxide (NO). Variants of endothelial nitric oxide synthase (eNOS) gene may lead to decreased NO levels. We explored the association between eNOS gene variants and nitric oxide levels among preeclamptic women in the Ghanaian population. This case-control study included 75 preeclamptic women and 75 healthy normotensive pregnant women attending antenatal care at the Nkawie-Toase Government Hospital, Ghana. A well-structured questionnaire was used to collect socio-demographic, obstetric and clinical data. Blood was obtained for DNA extraction; the gene variants were determined using PCR and RFLP. Preeclamptic women had significantly lower NO concentration compared to the normotensives (p < 0.0001) and was significantly different between VNTR variants (p < 0.0001). A significant difference in VNTR intron 4 distribution was also observed between the preeclamptic and normotensive women with 4c4c" (12.0%) and "4a4c" (1.3%) genotypes found predominantly in preeclamptic women (p < 0.0001). There was significantly higher distribution of "TC" genotype in preeclamptic women (44.0%) compared to normotensives (22.7%) (p = 0.019). However, possessing "4a4b" (cOR: 0.17, 95% CI 0.04-0.64) and "4b4b" (cOR: 0.09, 95% CI 0.02-0.38) significantly decreased the likelihood of experiencing preeclampsia by 83% and 91% respectively. Nitric oxide is reduced in preeclamptic women. NO levels in preeclampsia are altered by VNTR intron 4 variants but not T786C variants. Possessing VNTR intron 4 "4b" allele decreases the risk of PE while the "4c" allele increases the risk of PE. There is the need for eNOS variant screening and nitric oxide estimation among pregnant women for early prediction of women at risk of preeclampsia.