Female-specific hypertension loci on rat chromosome 13. Hypertension 2013 Sep;62(3):557-63
Date
07/03/2013Pubmed ID
23817491Pubmed Central ID
PMC3870583DOI
10.1161/HYPERTENSIONAHA.113.01708Scopus ID
2-s2.0-84883301077 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
Author List
Hoffman MJ, Flister MJ, Nunez L, Xiao B, Greene AS, Jacob HJ, Moreno CMESH terms used to index this publication - Major topics in bold
AllelesAnimals
Blood Pressure
Chromosome Mapping
Chromosomes, Mammalian
Female
Genetic Loci
Hypertension
Kidney
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Renin
