Open AccessVariable Transcriptional Regulation of the Human Aldosterone Synthase Gene Causes Salt-Dependent High Blood Pressure in Transgenic Mice
Author(s) -
Brahmaraju Mopidevi,
Meenakshi Kaw,
Nitin Puri,
Madhusudan Reddy Ponnala,
Sudhir Jain,
Anita Rana,
Narsimha Rao Keetha,
Sadik Khuder,
Steven Fiering,
Ashok Kumar
Publication year - 2014
Publication title -
circulation cardiovascular genetics
Language(s) - English
Resource type - Journals
eISSN - 1942-325X
pISSN - 1942-3268
DOI - 10.1161/circgenetics.114.000694
Subject(s) - aldosterone synthase , biology , haplotype , genetically modified mouse , transgene , single nucleotide polymorphism , gene , endocrinology , gene expression , candidate gene , aldosterone , medicine , microbiology and biotechnology , blood pressure , genetics , allele , genotype , renin–angiotensin system
Aldosterone, synthesized in the adrenal cortex by the enzyme CYP11B2, induces positive sodium balance and predisposes to hypertension. Various investigators, using genomic DNA analyses, have linked -344T polymorphism in the human CYP11B2 (hCYP11B2) gene to human hypertension. hCYP11B2 gene promoter has 3 single-nucleotide polymorphisms in linkage disequilibrium: T/A at -663, T/C at -470, and C/T at -344. Variants ACT occur together and form the haplotype-I (Hap-I), whereas variants TTC constitute Hap-II. We hypothesize that these single-nucleotide polymorphisms, when present together, will lead to haplotype-dependent differences in the transcriptional regulation of the hCYP11B2 gene and affect blood pressure regulation.
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