Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients
AuthorDuarte, Julio D.
Desai, Ankit A.
Arwood, Meghan J.
Yacob, Alex A.
Stamos, Thomas D.
Cavallari, Larisa H.
Zamanian, Roham T.
Shah, Sanjiv J.
Machado, Roberto F.
AffiliationUniv Arizona, Coll Med, Dept Med
Univ Arizona, Coll Med, Sarver Heart Ctr
MetadataShow full item record
PublisherSAGE PUBLICATIONS INC
CitationEndothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients, Julio D. Duarte, Mayank Kansal, Ankit A. Desai, Katherine Riden, Meghan J. Arwood, Alex A. Yacob, Thomas D. Stamos, Larisa H. Cavallari, Roham T. Zamanian, Sanjiv J. Shah, and Roberto F. Machado, Pulmonary Circulation, https://doi.org/10.1177/2045894018773049
RightsCopyright © 2018, © SAGE Publications
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AbstractThe biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role of NOS in HF-PH. DNA samples from 118 patients with HF-PH were genotyped for the NOS3 rs1799983 and NOS2 rs3730017 polymorphisms. A multiple regression model was used to compare hemodynamic measurements between genotype groups. Patients with the T/T genotype at rs1799983 possessed a nearly 10 mmHg increased transpulmonary gradient (TPG) compared to those with other genotypes (P = 0.006). This finding was replicated in an independent cohort of 94 HF-PH patients (P = 0.005). However, when tested in a cohort of 162 pre-capillary pulmonary arterial hypertension patients, no association was observed. In a combined analysis of both HF-PH cohorts, mean pulmonary artery pressure (mPAP), diastolic pulmonary gradient (DPG), and CpcPH status were also associated with rs1799983 genotype (P = 0.005, P = 0.03, and P= 0.02, respectively). In patients with HF-PH, the NOS3 rs1799983 polymorphism is associated with TPG, and potentially mPAP and DPG as well. These findings suggest that endothelial NOS (encoded by NOS3) may be involved in the pulmonary vascular remodeling observed in Cpc-PH and warrants further study.
Note12 month embargo; published online: 2 May 2018
VersionFinal published version
SponsorsNIH/NIGMS [K23 GM112014]; NIH/NHLBI [R01 HL141281, R01 HL111656, R01 HL127342, R01 HL133951]