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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.

Associations of NADPH oxidase-related genes with blood pressure changes and incident hypertension: The GenSalt Study