التفاصيل البيبلوغرافية
| العنوان: |
Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. |
| المؤلفون: |
Roberts KE, Fallon MB, Krowka MJ, Brown RS, Trotter JF, Peter I, Tighiouart H, Knowles JA, Rabinowitz D, Benza RL, Badesch DB, Taichman DB, Horn EM, Zacks S, Kaplowitz N, Kawut SM, Pulmonary Vascular Complications of Liver Disease Study Group, Roberts, Kari E, Fallon, Michael B, Krowka, Michael J |
| المصدر: |
American Journal of Respiratory & Critical Care Medicine; May2009, Vol. 179 Issue 9, p835-842, 8p |
| مستخلص: |
Rationale: Portopulmonary hypertension (PPHTN) occurs in 6% of liver transplant candidates. The pathogenesis of this complication of portal hypertension is poorly understood.Objectives: To identify genetic risk factors for PPHTN in patients with advanced liver disease.Methods: We performed a multicenter case-control study of patients with portal hypertension. Cases had a mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dynes.s(-1).cm(-5), and pulmonary capillary wedge pressure < or =15 mm Hg. Controls had a right ventricular systolic pressure < 40 mm Hg (if estimated) and normal right-sided cardiac morphology by transthoracic echocardiography. We genotyped 1,079 common single nucleotide polymorphisms (SNPs) in 93 candidate genes in each patient.Measurements and Main Results: The study sample included 31 cases and 104 controls. Twenty-nine SNPs in 15 candidate genes were associated with the risk of PPHTN (P < 0.05). Multiple SNPs in the genes coding for estrogen receptor 1, aromatase, phosphodiesterase 5, angiopoietin 1, and calcium binding protein A4 were associated with the risk of PPHTN. The biological relevance of one of the aromatase SNPs was supported by an association with plasma estradiol levels.Conclusions: Genetic variation in estrogen signaling and cell growth regulators is associated with the risk of PPHTN. These biologic pathways may elucidate the mechanism for the development of PPHTN in certain patients with severe liver disease. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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