Inducible nitric oxide synthase haplotype associated with hypertension and responsiveness to antihypertensive drug therapy

Hypertension is a multifactorial disorder associated with increased inducible nitric oxide synthase (iNOS) expression and activity. While genetic polymorphisms affect iNOS expression, it is not known whether iNOS gene polymorphisms affect the susceptibility to hypertension and the responses to antihypertensive therapy. This study aimed at assessing whether iNOS polymorphisms ((CCTTT)n, g.-1026C > A, and g.2087G > A) and haplotypes are associated with hypertension and with responsiveness to drug therapy. We studied 115 well controlled hypertensive patients (HTN), 82 hypertensive patients resistant to optimized antihypertensive therapy (RHTN), and 113 normotensive healthy subjects (NT). Genotypings were carried out using real-time polymerase chain reaction (PCR) and PCR amplification followed by capillary electrophoresis. The software PHASE 2.1 was used to estimate the haplotype frequencies in each group. Variant genotypes (GA + AA) for the g.2087G > A polymorphism were more commonly found in hypertensive patients (HTN + RHTN) than in normotensives (P = 0.016; OR = 2.05). We found no associations between genotypes and responsiveness to therapy (P > 0.05). The S-C-A haplotype was more commonly found in hypertensive patients (HTN + RHTN) than in normotensives (P = 0.014; OR = 6.07). Interestingly, this haplotype was more commonly found in the HTN group than in the RHTN group (P = 0.012; OR = 0.14). Our findings indicate that the g.2087G > A polymorphism in the iNOS gene affects the susceptibility to hypertension. Moreover, while the S-C-A haplotype is associated with hypertension, it is also associated with responsiveness to antihypertensive therapy.

► Inducible nitric oxide synthase (iNOS) contributes to experimental hypertension. ► Genetic polymorphisms affect iNOS expression and diseases susceptibility. ► We found an iNOS haplotype associated with hypertension. ► The same iNOS haplotype is associated with responsiveness to antihypertensives.