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    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Btg2Ratalbuminuria  IAGP  RGD 
FmodRatalbuminuria  IAGP  RGD 
OptcRatalbuminuria  IAGP  RGD 
PrelpRatalbuminuria  IAGP  RGD 
RenRatalbuminuria  IAGP  RGD 
SS.BN-(D13Hmgc64-RN34_13048990782)/McwiRatalbuminuria inducedIAGPcontrolled sodium content dietin maleRGD 
SS.BN-(D13Rat25-RN34_13048990782)/McwiRatalbuminuria sexual_dimorphismIAGPcontrolled sodium chloride content dietmore severe in maleRGD 
SS.BN-(D13Rat25-rs106935835)/McwiRatalbuminuria inducedIAGPcontrolled sodium content diet RGD 
SS.BN-(D13Rat25-rs198199323)/McwiRatalbuminuria sexual_dimorphismIAGPcontrolled sodium chloride content dietmore severe in maleRGD 
SS/JrHsdMcwiRatalbuminuria inducedIAGPcontrolled sodium chloride content diet RGD 
SS.BN-(D13Hmgc64-RN34_13048990782)/McwiRatdecreased mean systemic arterial blood pressure inducedIAGPcontrolled sodium content dietin female and compared to SS/JrHsdMcwiRGD 
SS.BN-(D13Rat25-RN34_13048990782)/McwiRatdecreased mean systemic arterial blood pressure sexual_dimorphismIAGPcontrolled sodium chloride content dietin female and compared to SS/JrHsdMcwiRGD 
SS.BN-(D13Rat25-rs198199323)/McwiRatdecreased mean systemic arterial blood pressure sexual_dimorphismIAGPcontrolled sodium chloride content dietin female and compared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc64-RN34_13048990782)/McwiRatdecreased urine albumin level inducedIAGPcontrolled sodium chloride content dietin female and compared to SS/JrHsdMcwiRGD 
SS.BN-(D13Rat25-RN34_13048990782)/McwiRatdecreased urine albumin level sexual_dimorphismIAGPcontrolled sodium chloride content dietin female and compared to SS/JrHsdMcwiRGD 
SS.BN-(D13Rat25-rs198199323)/McwiRatdecreased urine albumin level sexual_dimorphismIAGPcontrolled sodium chloride content dietin female and compared to SS/JrHsdMcwiRGD 
Btg2Ratsalt-sensitive hypertension  IAGP  RGD 
FmodRatsalt-sensitive hypertension  IAGP  RGD 
OptcRatsalt-sensitive hypertension  IAGP  RGD 
PrelpRatsalt-sensitive hypertension  IAGP  RGD 
RenRatsalt-sensitive hypertension  IAGP  RGD 
SS.BN-(D13Hmgc64-RN34_13048990782)/McwiRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content dietin maleRGD 
SS.BN-(D13Rat25-RN34_13048990782)/McwiRatsalt-sensitive hypertension sexual_dimorphismIAGPcontrolled sodium chloride content dietmore severe in male on 8% NaCl dietRGD 
SS.BN-(D13Rat25-rs106935835)/McwiRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content diet RGD 
SS.BN-(D13Rat25-rs198199323)/McwiRatsalt-sensitive hypertension sexual_dimorphismIAGPcontrolled sodium chloride content dietmore severe in male on 8% NaCl dietRGD 
SS/JrHsdMcwiRatsalt-sensitive hypertension inducedIAGPcontrolled sodium chloride content diet RGD 

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)

QTLs
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