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

TITLE=SLC12A3 Variation and Renal Function in Chinese Patients With Hypertension

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.863275

DOI=10.3389/fmed.2022.863275

ISSN=2296-858X

ABSTRACT=<sec><title>Objective</title><p><italic>SLC12A3</italic> (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 <italic>SLC12A3</italic> gene polymorphisms and renal function in patients with hypertension.</p></sec><sec><title>Methods</title><p>Participants from three non-diabetic hypertensive cohorts, including young-onset hypertension (cohort 1, <italic>n</italic> = 882), treatment-naïve hypertension (cohort 2, <italic>n</italic> = 90), and follow-up cohort (cohort 3, <italic>n</italic> = 166), underwent genotyping for single nucleotide polymorphisms in <italic>SLC12A3</italic>. Renal events were defined as a &gt;25 and &gt;50% decline in estimated glomerular filtration rate (eGFR).</p></sec><sec><title>Results</title><p>In cohort 1, <italic>SLC12A3</italic> rs16963397 C/C or C/G (<italic>P</italic> = 0.005), rs13334864 C/C or C/T (<italic>P</italic> = 0.020), and rs7187932 A/A or A/G polymorphisms (<italic>P</italic> = 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 <italic>SLC12A3</italic> rs16963397 C/C or rs13334864 C/C polymorphisms had more &gt;25 and &gt;50% eGFR decline than their counterparts (log-rank test, <italic>P</italic> = 0.058 and <italic>P</italic> = 0.038, respectively). Cox regression analysis revealed that <italic>SLC12A3</italic> rs16963397 C/C and rs13334864 C/C polymorphisms were significantly associated with an increased risk of &gt;25% [hazard ratio (HR), 3.294; 95% confidence interval (CI), 1.158–9.368; <italic>P</italic> = 0.025] and &gt;50% decline in eGFR (HR, 18.630; 95% CI, 1.529–227.005, <italic>P</italic> = 0.022) than their counterparts.</p></sec><sec><title>Conclusion</title><p><italic>SLC12A3</italic> polymorphisms are associated with renal function in Chinese patients with hypertension.</p></sec>