Female-specific hypertension loci on rat chromosome 13

Hypertension. 2013 Sep;62(3):557-63. doi: 10.1161/HYPERTENSIONAHA.113.01708. Epub 2013 Jul 1.


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 (line9BP3 and line9BP4) 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 (line9BP3) significantly lowered BP by 21 mm Hg on an 8% NaCl diet (153 ± 7 versus 174 ± 5 mm Hg; P<0.001). Unexpectedly, the addition of 23 kb of Brown Norway chromosome 13 (line9BP4) 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.

Keywords: blood pressure; genetics; hypertension; kidney; sex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Blood Pressure / genetics*
  • Chromosome Mapping
  • Chromosomes, Mammalian*
  • Female
  • Genetic Loci*
  • Hypertension / genetics*
  • Hypertension / metabolism
  • Kidney / metabolism
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Dahl
  • Renin / genetics


  • Renin