A Quantitative Trait Locus for Sodium-Lithium Countertransport Is Linked to Chromosome Four in Baboons
Alterations in cell sodium transport characteristics, such as red blood cell intracellular sodium (ICNa) levels and sodium-lithium countertransport (SLC), are secondary biochemical indices of a primary cell membrane abnormality that have been associated with some forms of essential hypertension. We are studying the effects of genes and environmental factors on hypertension and blood pressure-related phenotypes such as ICNa and SLC in baboons, a non-human primate model for blood pressure regulation. In a previous study of 84 baboons, systolic blood pressure increased with increasing ICNa (p = 0.002) and SLC (p = 0.06). In the current study, genotypes for 280 microsatellite loci, as well as SLC and ICNa data, were determined for 623 baboons comprising 11 pedigrees. The heritabilities of ICNa and SLC were 0.80±0.07 and 0.61±0.10, respectively. We performed a genome screen using a maximum-likelihood based, variance components linkage analysis program (SOLAR) and obtained evidence that a possible quantitative trait locus (QTL) for SLC is located on the baboon homologue of human chromosome 4 between D4S2456 and D4S2365 with a maximum multipoint lod-score = 8.76 (p< 10-10) at D4S1645. This QTL accounts for approximately 2/3 of the additive genetic variation in SLC in baboons. We found no evidence for linkage with ICNa. Thus, we have evidence that a gene located on human chromosome 4 (baboon chromosome 5) affects cell sodium transport in baboons. No strong candidate genes have yet been identified in this region. However, future studies to identify and characterize this gene may elucidate fundamental processes that contribute to the development of hypertension.