RGD Reference Report - Female-specific hypertension loci on rat chromosome 13. - Rat Genome Database

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Female-specific hypertension loci on rat chromosome 13.

Authors: Hoffman, Matthew J  Flister, Michael J  Nunez, Lizbeth  Xiao, Bing  Greene, Andrew S  Jacob, Howard J  Moreno, Carol 
Citation: Hoffman MJ, etal., Hypertension. 2013 Sep;62(3):557-63. doi: 10.1161/HYPERTENSIONAHA.113.01708. Epub 2013 Jul 1.
RGD ID: 12802368
Pubmed: PMID:23817491   (View Abstract at PubMed)
PMCID: PMC3870583   (View Article at PubMed Central)
DOI: DOI:10.1161/HYPERTENSIONAHA.113.01708   (Journal Full-text)

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.

Phenotype Annotations    

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Btg2  (BTG anti-proliferation factor 2)
Fmod  (fibromodulin)
Optc  (opticin)
Prelp  (proline and arginine rich end leucine rich repeat protein)
Ren  (renin)

Bp397  (Blood pressure QTL 397)
Bp398  (Blood pressure QTL 398)
Bp399  (Blood pressure QTL 399)

Objects referenced in this article
Marker rs106935835 rs106935835 Rattus norvegicus
Marker rs198199323 rs198199323 Rattus norvegicus
Marker RN34_13048990782 RN34_13048990782 Rattus norvegicus
Marker 4110 4110 Rattus norvegicus
Marker 4582 4582 Rattus norvegicus

Additional Information