Associations of NADPH Oxidase Related Genes with Blood Pressure Changes and Incident Hypertension: The GenSalt Study

Abstract

Previous studies have indicated that reactive oxygen species produced by NADPH oxidase (Nox) are important risk factors of hypertension. The current study aims to examine the associations of Nox related genes with longitudinal blood pressure (BP) changes and the risk of incident hypertension in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study. A total of 1,768 participants from 633 families were included in our analysis. Nine BP measurements were obtained in the morning at baseline and during two follow-up visits. The mixed-effect models were used to investigate the associations of 52 tagged single nucleotide polymorphisms in 11 Nox related genes with BP changes and incident hypertension. Gene-based analyses were performed by truncated product method (TPM) and Versatile Gene-based Association Study (VEGAS). Over the 7.2 years of follow-up, systolic BP (SBP) and diastolic BP (DBP) increased, and 32.1% (512) of participants developed hypertension. SNPs rs12094228, rs16861188 and rs12066019 in NCF2 were significantly associated with longitudinal change in SBP ( P _interaction = 1.1 × 10 ⁻³, 2.8 × 10 ⁻³ and 1.2 × 10 ⁻³, respectively). Gene-based analyses revealed that NCF2 was significantly associated with SBP ( P _TPM = 1.00 × 10 ⁻⁶, P _VEGAS = 1.26 × 10 ⁻⁴) and DBP changes ( P _TPM = 5.84 × 10 ⁻⁴, P _VEGAS = 1.04 × 10 ⁻³). These findings suggested that NCF2 may play an important role in BP changes over time in the Han Chinese population.