{"title":"Association of the single nucleotide polymorphism rs1697421 with an increased postprandial serum phosphorus level.","authors":"Sachi Nii-Nakayama, Misaki Katsumoto, Satono Ishitani, Yoko Narasaki, Chihiro Seko, Michiyo Yamasaki, Hirokazu Ohminami, Kohta Ohnishi, Masashi Masuda, Hisami Yamanaka-Okumura, Hironori Yamamoto, Yutaka Taketani","doi":"10.1007/s10157-025-02644-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>A high serum phosphorus (P) level is a risk factor for cardiovascular disease (CVD) and mortality in patients with chronic kidney disease (CKD). Moreover, increased postprandial serum P levels after high dietary P intake impair vascular endothelial function. Therefore, management of postprandial serum P levels is important in CKD patients. Recently, a genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with fasting serum P levels in individuals of European ancestry. However, the effects of these SNPs on postprandial serum P levels and vascular endothelial function remain unclear.</p><p><strong>Methods: </strong>A randomized, single-blind, crossover study in 99 healthy Japanese was performed to determine the association between SNPs and postprandial serum P levels, flow-mediated dilation (FMD) or alkaline phosphatase activity. The impact of SNP on gene transcriptional activity was also analyzed using in vitro experiment.</p><p><strong>Results: </strong>The participants who were TT homozygotes of SNP rs1697421 (located near the tissue nonspecific alkaline phosphatase [TNAP] gene) had higher postprandial serum P levels than C allele carriers. FMD was more significantly impaired in the TT homozygotes than in the CC homozygotes in men. In the in vitro experiment, TNAP transcriptional activity was significantly lower in TT homozygotes than in the others.</p><p><strong>Conclusion: </strong>These results suggest that in TT homozygotes of SNP rs1697421, hepatic P uptake is affected through changes in serum TNAP levels, leading to high postprandial serum P levels and impairment of FMD. The present findings can contribute to the development of gene-based therapeutic approaches for the management of serum P levels.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10157-025-02644-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：高血清磷（P）水平是慢性肾脏病（CKD）患者罹患心血管疾病（CVD）和死亡的风险因素。此外，饮食中摄入大量磷后，餐后血清磷水平升高会损害血管内皮功能。因此，控制餐后血清 P 水平对 CKD 患者非常重要。最近，一项全基因组关联研究发现了与欧洲血统个体空腹血清 P 水平相关的单核苷酸多态性（SNPs）。然而，这些 SNPs 对餐后血清 P 水平和血管内皮功能的影响仍不清楚：方法：对 99 名健康日本人进行了一项随机、单盲、交叉研究，以确定 SNP 与餐后血清 P 水平、血流介导的扩张（FMD）或碱性磷酸酶活性之间的关系。此外，还通过体外实验分析了 SNP 对基因转录活性的影响：结果：SNP rs1697421（位于组织非特异性碱性磷酸酶[TNAP]基因附近）的TT等位基因携带者餐后血清P水平高于C等位基因携带者。与 CC 等位基因携带者相比，男性 TT 等位基因携带者的 FMD 明显受损。在体外实验中，TT 同型基因携带者的 TNAP 转录活性明显低于其他人：这些结果表明，在 SNP rs1697421 的 TT 基因同系基因携带者中，肝脏对 P 的吸收会通过血清 TNAP 水平的变化而受到影响，从而导致餐后血清 P 水平升高和 FMD 受阻。本研究结果有助于开发基于基因的治疗方法来控制血清 P 水平。
Association of the single nucleotide polymorphism rs1697421 with an increased postprandial serum phosphorus level.
Background: A high serum phosphorus (P) level is a risk factor for cardiovascular disease (CVD) and mortality in patients with chronic kidney disease (CKD). Moreover, increased postprandial serum P levels after high dietary P intake impair vascular endothelial function. Therefore, management of postprandial serum P levels is important in CKD patients. Recently, a genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with fasting serum P levels in individuals of European ancestry. However, the effects of these SNPs on postprandial serum P levels and vascular endothelial function remain unclear.
Methods: A randomized, single-blind, crossover study in 99 healthy Japanese was performed to determine the association between SNPs and postprandial serum P levels, flow-mediated dilation (FMD) or alkaline phosphatase activity. The impact of SNP on gene transcriptional activity was also analyzed using in vitro experiment.
Results: The participants who were TT homozygotes of SNP rs1697421 (located near the tissue nonspecific alkaline phosphatase [TNAP] gene) had higher postprandial serum P levels than C allele carriers. FMD was more significantly impaired in the TT homozygotes than in the CC homozygotes in men. In the in vitro experiment, TNAP transcriptional activity was significantly lower in TT homozygotes than in the others.
Conclusion: These results suggest that in TT homozygotes of SNP rs1697421, hepatic P uptake is affected through changes in serum TNAP levels, leading to high postprandial serum P levels and impairment of FMD. The present findings can contribute to the development of gene-based therapeutic approaches for the management of serum P levels.
期刊介绍：
Clinical and Experimental Nephrology is a peer-reviewed monthly journal, officially published by the Japanese Society of Nephrology (JSN) to provide an international forum for the discussion of research and issues relating to the study of nephrology. Out of respect for the founders of the JSN, the title of this journal uses the term “nephrology,” a word created and brought into use with the establishment of the JSN (Japanese Journal of Nephrology, Vol. 2, No. 1, 1960). The journal publishes articles on all aspects of nephrology, including basic, experimental, and clinical research, so as to share the latest research findings and ideas not only with members of the JSN, but with all researchers who wish to contribute to a better understanding of recent advances in nephrology. The journal is unique in that it introduces to an international readership original reports from Japan and also the clinical standards discussed and agreed by JSN.
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