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

Journal of Human Hypertension volume 32, pages 287–293 (2018)Cite this article

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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 (Pinteraction = 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 (PTPM = 1.00 × 10−6, PVEGAS = 1.26 × 10−4) and DBP changes (PTPM = 5.84 × 10−4, PVEGAS = 1.04 × 10−3). These findings suggested that NCF2 may play an important role in BP changes over time in the Han Chinese population.

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Acknowledgements

This study is supported by the National Natural Science Foundation of China (81570386, 91439202, 91643208 and 81600332) and the CAMS Innovation Fund for Medical Sciences (grants no. 2017-I2M-1–004 and 2016-I2M-2–001). The GenSalt study is supported by a cooperative agreement project grant (U01HL072507, R01HL087263, and R01HL090682) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

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  1. These authors contributed equally: Hongfan Li and Xikun Han.

Authors and Affiliations

  1. Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China

    Hongfan Li, Xikun Han, Zunsong Hu, Jianfeng Huang, Dongfeng Gu & Shufeng Chen

  2. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, 70112, USA

    Jing Chen & Jiang He

  3. Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX, USA

    James E. Hixson

  4. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA

    Dabeeru C. Rao

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  1. Hongfan Li
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Correspondence to Shufeng Chen.

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Li, H., Han, X., Hu, Z. et al. Associations of NADPH oxidase-related genes with blood pressure changes and incident hypertension: The GenSalt Study. J Hum Hypertens 32, 287–293 (2018). https://doi.org/10.1038/s41371-018-0041-6

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