Abstract
BACKGROUND: Sodium-lithium countertransport (SLC) activity, an intermediate phenotype of essential hypertension, has been linked to a region of baboon chromosome 5, homologous to human chromosome 4p. Human SLC34A2, located at chromosome 4p15.1-p15.3, is a positional candidate gene for SLC. The specific aim of this study was to identify genetic variants of the SLC34A2 gene in both baboon and human, and to examine the relationship of these polymorphisms with SLC activity and blood pressure. METHODS: Single-nucleotide polymorphism (SNP) was identified by sequencing the SLC34A2 gene in 24 baboon founders and 94 unrelated individuals. All tag SNPs in SLC34A2 were genotyped in 1,856 individuals from 252 pedigrees of mixed European ancestry. Three SNPs in baboon were genotyped in 634 baboons comprising 11 pedigrees. RESULTS: In human, one SNP (rs12501856) was found to be significantly associated with SLC individually, though it did not pass multiple testing correction; however, haplotype 2 containing allele C of SNP rs12501856 showed strong evidence of association with SLC (P = 0.0037) after multiple comparison adjustment. This haplotype was also marginally associated with diastolic blood pressure and systolic blood pressure. This finding was confirmed in baboons, where a highly significant association was detected between SLC and baboon SNP Asn136Asn (P = 0.0001). However, the associated SNP did not account for the linkage signal on baboon chromosome 5. CONCLUSIONS: Consistent results in two different species imply that SLC34A2 is associated with SLC activity and blood pressure.