Female-Specific Hypertension Loci on Rat Chromosome 13

A 3.7-Mb region of rat chromosome 13 (45.2–49.0 Mb) affects blood pressure (BP) in females only, indicating the presence of sex-specific BP loci in close proximity to the Renin locus. In the present study, we used a series of Dahl salt-sensitive/Mcwi-13 Brown Norway congenic rat strains to further resolve BP loci within this region. We identified 3 BP loci affecting female rats only, of which the 2 smaller loci (line9 BP3 and line9 BP4 ) were functionally characterized by sequence and expression analysis. Compared with SS (SS/HsdMcwiCrl), the presence of a 591-kb region of BN (BN/NHsdMcwi) chromosome 13 (line9 BP3 ) significantly lowered BP by 21 mm Hg on an 8% NaCl diet (153±7 versus 174±5 mm Hg; P BP4 ) completely erased the female-specific BP protection on 8% NaCl diet, suggesting that BN hypertensive allele(s) reside in this region. The congenic interval of the protective line 9F strain contains 3 genes ( Optc , Prelp , and Fmod ), and the hypertensive line 9E contains 1 additional gene ( Btg2 ). Sequence analysis of the 2 BP loci revealed a total of 282 intergenic variants, with no coding variants. Analysis of gene expression by quantitative real-time polymerase chain reaction revealed strain- and sex-specific differences in Prelp , Fmod , and Btg2 expression, implicating these as novel candidate genes for female-specific hypertension.