Mapping a genetic biomarker of blood pressure to <807.3kb using two genetically hypertensive rats

Two of the most widely used strains for mapping quantitative trait loci (QTLs) for blood pressure (BP) are the Dahl Salt‐sensitive (S) rat and the Spontaneously Hypertensive Rat (SHR). To map a previously identified BP QTL that differentiate these two strains, we continued substitution mapping studies on a BP QTL on chromosome 9 identified by a linkage study. A total of 11 new congenic substrains were developed and characterized. BP and heart weights of two of these substrains with introgressed segments of 2.05Mb and 807.3Kb were both significantly (p<0.001) lower than that of the S by 56 ± 6.61 and 41 ± 8.55 mm Hg (p<0.001)), respectively. The mRNA and protein levels of Tmeff2 were lower in the congenic substrain spanning 2.05Mb. Further, because Tmeff2 was the only protein‐coding candidate gene within the substrain spanning 807.3kb, which also had a BP effect, it was prioritized as a candidate gene. Tmeff2 is known to be upregulated in patients from multiple cohorts with cardiac hypertrophy. Because Tmeff2 is also known to affect cell proliferation, we assessed the proliferation rates of cells obtained from S and the congenic substrains with BP effect. Proliferation of cardiac fibroblasts was significantly slower in the congenic compared with S (p<0.05). Taken together, these results suggest that variants within the 807.3Kb congenic segment that alter the expression of Tmeff2 can be prioritized as candidate biomarkers controlling blood pressure and associated cardiac hypertrophy in both rats and in humans.