Association Between SLC20A1 and Sodium-Lithium Countertransport

Background Sodium-lithium countertransport (SLC) is a premorbidity marker of essential hypertension. Evidence from linkage analysis and kinetic studies in humans have suggested that SLC20A1 variations may affect SLC activity as measured in erythrocytes and leukocytes. SLC20A1 encodes a sodium-dependent phosphate cotransporter, and is widely expressed on the mammalian plasma membrane. In this study, we investigated the relationship between SLC20A1 and SLC activity. Methods By means of gene expression profiling, we studied the expressions of SLC20A1 in individuals with high SLC activity as compared to those with low SLC activity. In order to investigate the allelic association of SLC20A1 with SLC, we genotyped six tag single-nucleotide polymorphisms (tSNPs) in SLC20A1 in subjects from the Rochester Family Heart Study (RFHS) involving 1,815 individuals from 252 pedigrees of mixed European ancestry. The genetic association of SLC20A1 with SLC was assessed by Sequential Oligogenic Linkage Analysis Routines (SOLAR). Results Expression levels of SLC20A1 were higher in individuals with high SLC activity than in those with low SLC activity. Four SNPs in SLC20A1 were associated with SLC activity after adjusting for age, sex, body mass index, triglycerides, and antihypertensive drug treatment (P ≤ 0.05). The strongest evidence of association was in respect of rs4849091 (P = 0.001), and this association remained significant even after correction for multiple tests. Conclusions Allelic variations in SLC20A1 were associated with the levels of SLC activity, thereby supporting the hypothesis that SLC20A1 is involved in determining SLC activity. American Journal of Hypertension advance online publication 28 July 2011; doi:10.1038/ajh.2011.130