SLC12A3 Variation and Renal Function in Chinese Patients With Hypertension

Chin-Chou Huang; Chia-Min Chung; Chih-Yu Yang; Hsin-Bang Leu; Po-Hsun Huang; Liang-Yu Lin; Tao-Cheng Wu; Shing-Jong Lin; Wen-Harn Pan; Jaw-Wen Chen

doi:10.3389/fmed.2022.863275

SLC12A3 Variation and Renal Function in Chinese Patients With Hypertension

Front Med (Lausanne). 2022 Jun 21:9:863275. doi: 10.3389/fmed.2022.863275. eCollection 2022.

Authors

Chin-Chou Huang^{1

2

3

4}, Chia-Min Chung^{5

6}, Chih-Yu Yang^{2

7

8}, Hsin-Bang Leu^{1

2

4

9}, Po-Hsun Huang^{1

4

7

10}, Liang-Yu Lin^{2

4

11}, Tao-Cheng Wu^{1

2

4}, Shing-Jong Lin^{1

4

7

12}, Wen-Harn Pan^{13

14}, Jaw-Wen Chen^{1

3

4

9}

Affiliations

¹ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
² School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁴ Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁵ Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan.
⁶ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁷ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁸ Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁹ Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁰ Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹¹ Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹² Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan.
¹³ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
¹⁴ Institute of Epidemiology, School of Public Health, National Taiwan University, Taipei, Taiwan.

Abstract

Objective: SLC12A3 (solute carrier family 12 member 3) gene variants are associated with diabetic nephropathy; however, their association with hypertensive nephropathy remains unknown. We aimed to investigate the association between SLC12A3 gene polymorphisms and renal function in patients with hypertension.

Methods: Participants from three non-diabetic hypertensive cohorts, including young-onset hypertension (cohort 1, n = 882), treatment-naïve hypertension (cohort 2, n = 90), and follow-up cohort (cohort 3, n = 166), underwent genotyping for single nucleotide polymorphisms in SLC12A3. Renal events were defined as a >25 and >50% decline in estimated glomerular filtration rate (eGFR).

Results: In cohort 1, SLC12A3 rs16963397 C/C or C/G (P = 0.005), rs13334864 C/C or C/T (P = 0.020), and rs7187932 A/A or A/G polymorphisms (P = 0.014) had higher eGFRs compared to their counterparts, with similar findings observed in cohort 2. In cohort 3, over a mean follow-up of 5.8 ± 1.7 years, participants with either SLC12A3 rs16963397 C/C or rs13334864 C/C polymorphisms had more >25 and >50% eGFR decline than their counterparts (log-rank test, P = 0.058 and P = 0.038, respectively). Cox regression analysis revealed that SLC12A3 rs16963397 C/C and rs13334864 C/C polymorphisms were significantly associated with an increased risk of >25% [hazard ratio (HR), 3.294; 95% confidence interval (CI), 1.158-9.368; P = 0.025] and >50% decline in eGFR (HR, 18.630; 95% CI, 1.529-227.005, P = 0.022) than their counterparts.

Conclusion: SLC12A3 polymorphisms are associated with renal function in Chinese patients with hypertension.

Keywords: SLC12A3; glomerular filtration rate; glomerular hyperfiltration; hypertension; hypertensive nephropathy.