This month in The American Journal of Human Genetics, researchers from Columbia University and the New York Psychiatric Institute present evidence that patients with familial primary pulmonary hypertension (PPH) have mutations in the bone morphogenetic protein receptor II (BMPR2) gene. PPH is a very serious, progressive condition characterized by lesions that cause constriction of the pulmonary arterial blood vessels. The resulting hypertension leads to heart failure and death, generally within 3 years of diagnosis. Current treatments require continuous administration of intravenous or inhaled medication, and they prolong survival but do not cure the disorder.
Sporadic cases of PPH are more common than familial cases, and their development can be associated with several things including: pregnancy, hypothyroidism, and the use of oral contraceptives, cocaine, or the appetite suppressant drugs, phentermine-fenfluramine (phen-fen). Phen-fen is no longer available in combination due to these effects. People with autoimmune disease or late stage AIDS can also develop PPH. Although the majority of PPH cases do not appear to have a primary genetic basis, the pathologies of both the sporadic and genetic forms of PPH are common.
BMPR2 is a cell signaling protein that plays a role in lung development, and the mutations found in patients with PPH are believed to reduce signaling in the BMP pathway. This, in turn, could lead to the overproliferation of cells, in pulmonary arterioles, that is characteristic of PPH. The overproliferation of smooth muscle cells leads to progressive muscularization of normally non-muscular parts of the blood vessels, thereby allowing these newly musculated parts to vasoconstrict. This increased vasoconstriction leads to hypertension.
The discovery of genes involved in familial PPH is extremely important because it will help doctors to better identify those at risk for developing this disorder. At-risk individuals could receive earlier and more aggressive therapy in an attempt to delay the age of onset and prolong survival. Identification of these genes will also help researchers to understand the basic cause of PPH and to unravel the pathways involved its development. This, in turn, will lead to improved treatments, and hopefully a cure, for both the familial and sporadic forms of this disorder.
For the full text of this article entitled "Familial Primary Pulmonary Hypertension (PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene", please see the latest articles section of The American Journal of Human Genetics website at www.ajhg.org.
This research was supported by grant from the National Heart, Lung and Blood Institute, Office of Clinical Trials at Columbia University, and United Therapeutics, Inc.
For further information, contact the corresponding author: Dr. James Knowles, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, 1051 Riverside Dr., Room 5916, Unit #28, New York, NY 10032. Phone: (212)543-5867. Fax: (212)543-6211. Email: firstname.lastname@example.org
Contributed by: Kate Beauregard, The American Journal of Human Genetics. Phone: (404)712-9985. Email: email@example.com
Message posted by: Kate Beauregard
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