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Associations of SGLT2 genetic polymorphisms with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults

Hypertension Research volume 46, pages 1795–1803 (2023)Cite this article

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers blood pressure (BP) and exert a salutary effect on the salt sensitivity of BP. This study aimed to examine the associations of SGLT2 genetic variants with salt sensitivity, longitudinal BP changes and the risk of incident hypertension in Baoji Salt-Sensitive Study. A total of 514 participants were recruited when the cohort was established in 2004, and 333 participants received a dietary intervention that consisted of a 3-day usual diet followed sequentially by a 7-day low-salt diet and a 7-day high-salt diet. The cohort was then followed up for 14 years to evaluate the longitudinal BP changes and development of hypertension. We found that SGLT2 SNP rs3813007 was significantly associated with the systolic BP (SBP) responses to the low-salt diet. Over the 14 years of follow-up, SNPs rs3116149 and rs3813008 were significantly associated with the longitudinal SBP changes, and SNPs rs3116149, rs3813008, rs3813007 in SGLT2 were significantly associated with incidence of hypertension. Furthermore, gene-based analyses revealed that SGLT2 was significantly associated with hypertension incidence. Our study suggests that SGLT2 genetic polymorphisms may be involved in salt sensitivity and development of hypertension.

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Acknowledgements

The authors are grateful to the grassroots health staff in Meixian Hospital of Traditional Chinese Medicine for providing administrative and technical support during the follow-up.

Funding

This work was supported by the National Natural Science Foundation of China No. 82070437, 81870319 (J-JM), 81600327 (YW) and 82070549 (HL), Natural Science Basic Research Program of Shanxi Province (2021JM-257, 2021JM-588), the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University of China No. XJTU1AF-CRF-2019-004 (J-JM) and XJTU1AF-CRF-2022-002, XJTU1AF2021CRF-021 (YW), Basic-Clinical Integration Innovation Project in Medicine of Xi’an Jiaotong University (YXJLRH2022009), Institutional Foundation of the First Affiliated Hospital of Xi’an Jiaotong University No. 2022MS-36, 2021ZXY-14, Key R&D Projects in Shaanxi Province Grant No. 2023-ZDLSF-50; the Chinese Academy of Medical Sciences & Peking Union Medical College (2017-CXGC03-2) and International Joint Research Center for Cardiovascular Precision Medicine of Shaanxi Province (2020GHJD-14).

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Author notes

  1. These authors contributed equally: Hao Jia, Peng Bao, Shi Yao.

Authors and Affiliations

  1. Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Hao Jia, Xi Zhang, Jian-Jun Mu, Gui-Lin Hu, Ming-Fei Du, Chao Chu, Yue-Yuan Liao, Dan Wang, Qiong Ma, Yu Yan, Ze-Jiaxin Niu & Yang Wang

  2. Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi’an, China

    Hao Jia, Jian-Jun Mu, Chao Chu, Yue-Yuan Liao, Dan Wang, Qiong Ma, Yu Yan & Yang Wang

  3. Department of General Practice, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Peng Bao

  4. National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Shi Yao

  5. Department of Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Xiao-Yu Zhang & Hao Li

  6. Department of Cardiology, Xi’an International Medical Center Hospital, Xi’an, China

    Lan Wang

  7. Department of Cardiology, Xi’an No.1 Hospital, Xi’an, China

    Wei-Hua Gao

  8. Department of Cardiology, Xi’an Central Hospital of Xi’an Jiaotong University, Xi’an, China

    Guan-Ji Wu

  9. Department of Medicine, Yale University School of Medicine, New Haven, CT, USA

    John Chang

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Jia, H., Bao, P., Yao, S. et al. Associations of SGLT2 genetic polymorphisms with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults. Hypertens Res 46, 1795–1803 (2023). https://doi.org/10.1038/s41440-023-01301-2

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