Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Hypertension early onset (Early-onset hypertension) - Gen NR3C2 (mineralocorticoid receptor)

Aldosterone, under normal conditions, has a high affinity for the mineralocorticoid receptor (MR), allowing the renal sodium reabsorption increasing blood pressure. In fact, in response to aldosterone, MR undergoes conformational changes, is translocated across the nuclear membrane and regulates transcription of certain genes to enhance sodium transport.

As a result, changes in the gene sequence NR3C2, located on the long arm of chromosome 4 (4q31.1), the mineralocorticoid receptor encoding can change blood pressure by impaired renal absorption of salt. This protein is important in regulating the amount of sodium in the body. Sodium regulation plays a role in controlling blood pressure and fluid balance. Certain hormones called mineralocorticoid bind to, and activate, the mineralocorticoid receptor. Aldosterone is a mineralocorticoid that activate the mineralocorticoid receptor. Mineralocorticoid receptor activated acts as a transcription factor that regulates proteins that control the transport of sodium or potassium in the cells. When sodium concentrations in the body are low, the mineralocorticoid receptor increases the number and activity of these proteins in the cell membrane, especially in certain cells of the kidney. These proteins help maintain sodium in the body through reabsorption and potassium removed by secretion.

A particular mutation in the gene can cause hypertension NR3C2 early onset with severe exacerbation during pregnancy. The mutation involved replaced by the amino acid serine in the amino acid leucine position 810 of the protein (or Ser810Leu S810L). This mutation generates a gain responsible for early onset hypertension function, especially prevalent during pregnancy, given the significant increase in renal uptake of salt and blood pressure and a marked suppression of aldosterone secretion. This occurs because all steroids, including progesterone , which in the unmutated mineralocorticoid receptor plays a role antagonist , are able to activate the mineralocorticoid receptor with S810L mutation. Early onset hypertension has a high incidence of cardiac death before age 50 and above described symptoms before age 20.

Hypertension early onset is inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed.

Tests in IVAMI: in IVAMI perform detection of mutations associated with early onset hypertension, by complete PCR amplification of the exons of the gene NR3C2, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).