Impact of the NOS3 intron 4 VNTR polymorphism on essential hypertension susceptibility in Algerian women

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.