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PHARMACOGENOMICS IN PULMONARY ARTERIAL HYPERTENSION

Award Number: R01HL078946
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2005
PERIOD OF PERFORMANCE END DATE: 07/31/2009

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PHARMACOGENOMICS IN PULMONARY ARTERIAL HYPERTENSION - DESCRIPTION (provided by applicant): Our goal is to determine clinically in PAH patients if associations exist between the efficacy and toxicity of sitaxsentan and bosentan and several gene polymorphisms in several key disease-specific and therapy specific genes. We will also characterize the relationship between these polymorphisms and PAH severity using either baseline hemodynamic or clinical surrogates for disease severity. Hypothesis: Polymorphisms influence the efficacy and toxicity of specific PAH therapy as well as development/severity of PAH via, their effect on PA remodeling, drug response or metabolism. This proposal will make use of a large population of well defined patients with PAH who were enrolled in several large clinical trials including Encysive protocols FPH02, 02x, 03 and 06 and a prospective cohort from four large PAH Centers. The sum total number of patients will be approximately 920, including 550 with PPH. This worldwide effort constitutes the largest clinical study of this deadly disease and in as such has great potential to alter clinical practice by revealing novel gene-drug interactions. We will test this hypothesis by executing the following Aims: Aim 1: Determine in PPH the relationship between known disease-specific polymorphisms (Serotorin transporter gene and PAI Hindlll) and variants in BMPR2 and SMAD4 with several well defined clinical efficacy endpoints of sitaxsentan and bosentan therapy. Aim 2: Determine in PAH the relationship between existing potentially "therapy-specific" polymorphism in the ET-1, ETAR, ETBR, NPR-c, prostacyclin receptor and prostacyclin synthase genes with several defined clinical efficacy endpoints of sitaxsentan and bosentan therapy. PAH = pulmonary arterial hypertension PA = pulmonary artery PPH = primary pulmonary hypertension


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2008 ( Subtotal = $451,702 )
2008	2008	ALLEGHENY SINGER RESEARCH CORP	2 ALLEGHENY CTR, 11TH FLOOR	PITTSBURGH	PA	15212	ALLEGHENY	USA	Lung Diseases Research	000	4	7/7/2008	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$451,702
														Subtotal = $451,702

Issue Date FY: 2007 ( Subtotal = $445,556 )
2007	2007	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	3	7/5/2007	NON-COMPETING CONTINUATION	$445,556
														Subtotal = $445,556

Issue Date FY: 2006 ( Subtotal = $450,628 )
2006	2006	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	2	6/24/2006	NON-COMPETING CONTINUATION	$450,628
														Subtotal = $450,628

Issue Date FY: 2005 ( Subtotal = $463,417 )
2005	2005	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	1	9/2/2005	NEW	$463,417
														Subtotal = $463,417

Grand Total All Awards = $1,811,303

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PHARMACOGENOMICS IN PULMONARY ARTERIAL HYPERTENSION

Award Number: R01HL078946

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2005

PERIOD OF PERFORMANCE END DATE: 07/31/2009

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