Association of the single nucleotide polymorphism rs1697421 with an increased postprandial serum phosphorus level

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.

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.

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.

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.