Estrogen Signaling and Portopulmonary Hypertension: The Pulmonary Vascular Complications of Liver Disease Study (PVCLD2). Issue 2 (29th September 2020)

• Record Type: Journal Article
• Authors: Al‐Naamani, Nadine; Krowka, Michael J.; Forde, Kimberly A.; Krok, Karen L.; Feng, Rui; Heresi, Gustavo A.; Dweik, Raed A.; Bartolome, Sonja; Bull, Todd M.; Roberts, Kari E.; Austin, Eric D.; Hemnes, Anna R.; Patel, Mamta J.; Oh, Jae K.; Lin, Grace; Doyle, Margaret F.; Denver, Nina; Andrew, Ruth; MacLean, Margaret R.; Fallon, Michael B.; Kawut, Steven M.
• Other Names: Timmerman Kasi investigator.; Mottram C.D. investigator.; Scanlon Paul D. investigator.; Miller Adam investigator.; Visnaw Karen investigator.; Homer Natalie investigator.; Andrew Ruth investigator.; Abbott Cheryl investigator.; Palevsky Harold I. investigator.; Rajender Reddy K. investigator.; Goldberg David S. investigator.; Khungar Vandana investigator.; Akaya Smith K. investigator.; Fritz Jason S. investigator.; Lynch Marita investigator.; Sharkoski Tiffany investigator.; Pinder Diane investigator.; Machicao Victor investigator.; Rubin Moises Nevah investigator.; Walker Kim investigator.; Cranford Stacy investigator.; Varing Jordan investigator.; Banga Namrata investigator.; Igenoza Oluwatosin investigator.; LaRochelle Celeste investigator.
• Is Part Of: Hepatology. Volume 73:Issue 2(2021)
• Page Start: 726
• Page End: 737
• Publication Date: 2020-09-29
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.31314
• Languages: English
• ISSNs: 0270-9139

Abstract

Abstract : Background and Aims: Portopulmonary hypertension (POPH) was previously associated with a single‐nucleotide polymorphism (SNP) rs7175922 in aromatase (cytochrome P450 family 19 subfamily A member 1 [ CYP19A1 ]). We sought to determine whether genetic variants and metabolites in the estrogen signaling pathway are associated with POPH. Approach and Results: We performed a multicenter case‐control study. POPH patients had mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dyn‐sec/cm −5, and pulmonary artery wedge pressure ≤15 mm Hg without another cause of pulmonary hypertension. Controls had advanced liver disease, right ventricular (RV) systolic pressure <40 mm Hg, and normal RV function by echocardiography. We genotyped three SNPs in CYP19A1 and CYP1B1 using TaqMan and imputed SNPs in estrogen receptor 1 using genome‐wide markers. Estrogen metabolites were measured in blood and urine samples. There were 37 patients with POPH and 290 controls. Mean age was 57 years, and 36% were female. The risk allele A in rs7175922 ( CYP19A1 ) was significantly associated with higher levels of estradiol ( P = 0.02) and an increased risk of POPH (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.12‐4.91; P = 0.02) whereas other SNPs were not. Lower urinary 2‐hydroxyestrogen/16‐α‐hydroxyestrone (OR per 1‐ln decrease = 2.04; 95% CI, 1.16‐3.57; P = 0.01), lower plasma levels of dehydroepiandrosterone‐sulfate (OR per 1‐ln decrease = 2.38; 95% CI, 1.56‐3.85; P < 0.001), and higher plasma levels of 16‐α‐hydroxyestradiol (OR per 1‐ln increase = 2.16; 95% CI, 1.61‐2.98; P < 0.001) were associated with POPH. Conclusions: Genetic variation in aromatase and changes in estrogen metabolites were associated with POPH.