Details

Autor(en) / Beteiligte

• 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.
• Timmerman, Kasi
• Mottram, C.D.
• Scanlon, Paul D.
• Miller, Adam
• Visnaw, Karen
• Homer, Natalie
• Abbott, Cheryl
• Palevsky, Harold I.
• Rajender Reddy, K.
• Goldberg, David S.
• Khungar, Vandana
• Akaya Smith, K.
• Fritz, Jason S.
• Lynch, Marita
• Sharkoski, Tiffany
• Pinder, Diane
• Machicao, Victor
• Rubin, Moises Nevah
• Walker, Kim
• Cranford, Stacy
• Varing, Jordan
• Banga, Namrata
• Igenoza, Oluwatosin
• LaRochelle, Celeste

Titel

Estrogen Signaling and Portopulmonary Hypertension: The Pulmonary Vascular Complications of Liver Disease Study (PVCLD2)

Ist Teil von

• Hepatology (Baltimore, Md.), 2021-02, Vol.73 (2), p.726-737

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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.