Impact of the NOS3 intron 4 VNTR polymorphism on essential hypertension susceptibility in Algerian women
TL;DR
It is suggested that the NOS3 intron 4 VNTR polymorphism is independently associated with susceptibility to essential hypertension in Algerian women, however, further validation in larger, independent cohorts is required.
Abstract
This study tests the hypothesis that the endothelial nitric oxide synthase (NOS3) intron 4 VNTR polymorphism is a significant genetic determinant of essential hypertension susceptibility within the Algerian population. A case-control study involving 221 participants (93 hypertensive patients and 128 controls) was conducted using PCR-based genotyping and multivariable logistic regression with stringent Bonferroni correction. Results revealed a significant association between the 4a allele and increased hypertension risk. This association was particularly robust in the female subgroup, where 4a carriers exhibited a 3.7-fold increased risk (OR=3.74, 95% CI: 1.88-7.70, P<0.0001). After adjusting for age and body mass index, both dominant and additive genetic models remained highly significant in women, even after applying the Bonferroni correction (P<0.001). Furthermore, integrating the NOS3 genotype with conventional risk factors improved predictive performance in the female cohort, increasing the area under the curve from 0.61 to 0.73 (DeLong’s P=0.0074), with 82.8% specificity. No significant association was observed in males, likely due to limited statistical power. These findings suggest that the NOS3 intron 4 VNTR polymorphism is independently associated with susceptibility to essential hypertension in Algerian women. However, further validation in larger, independent cohorts is required.