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Identification of Btg2 as a candidate gene for hypertension in females
Author(s) -
Hoffman Matthew J.,
Xiao Bing,
Nunez Lizbeth,
Flister Michael,
Moreno Carol
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.955.7
Subject(s) - congenic , renal cortex , gene , renal medulla , endocrinology , biology , candidate gene , medicine , western blot , medullary cavity , microbiology and biotechnology , kidney , genetics
We previously found that transfer of a 3.7 Mbp region of chromosome 13 (Chr13) from the normotensive Brown Norway (BN) rat into the hypertensive Dahl salt‐sensitive (SS) rat attenuates the development of salt‐sensitive hypertension in female but not in male rats. We sought to identify the causative gene by developing and phenotyping narrow congenic strains, and by sequence and gene expression analysis of the candidate region. We created two congenic lines with BN substitutions differing by 23 Kb. The congenic regions differ by only one gene, Btg2 , and have 35 sequence variants. Mean arterial pressure (MAP), measured by telemetry, was not different between strains in males after 3 weeks of 8% NaCl diet, while female with Btg2 BN had significantly higher MAP (186±3.1 mmHg) than Btg2 SS females (151±5.8mmHg). Btg2 BN females had also significantly higher protein excretion than Btg2 SS and two‐fold increase on renal medullary fibrosis. Btg2 mRNA expression was determined by qRT‐PCR in renal cortex and medulla, and BTG2 protein expression was subsequently assessed by western blot. Males had no differences in expression in renal cortex or medulla, but females had significant differences in cortex ( Btg2 BN : 1.8±0.2 fold change, Btg2 SS : 0.4±.01). Our data suggest that Btg2 is a candidate gene salt‐sensitive hypertension in females.