Estrogen Signaling and Portopulmonary Hypertension: The Pulmonary Vascular Complications of Liver Disease Study (PVCLD2).
Estrogen Signaling and Portopulmonary Hypertension: The Pulmonary Vascular Complications of Liver Disease Study (PVCLD2).
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雌激素信号传导和门脉性肺动脉高压：肝病肺血管并发症研究 (PVCLD2)。
DOI：
10.1002/hep.31314
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
, for the Pulmonary Vascular Complications of Liver Disease Study Group
中科院分区：
文献类型：
--
作者：
Al-Naamani N;Krowka MJ;Forde KA;Krok KL;Feng R;Heresi GA;Dweik RA;Bartolome S;Bull TM;Roberts KE;Austin ED;Hemnes AR;Patel MJ;Oh JK;Lin G;Doyle MF;Denver N;Andrew R;MacLean MR;Fallon MB;Kawut SM;, for the Pulmonary Vascular Complications of Liver Disease Study Group
门静脉高压症(POPH)与芳香族酶(CYP19A1)的单核苷酸多态(SNP)rs7175922相关。我们试图确定雌激素信号通路中的遗传变异和代谢物是否与POPH相关。我们进行了一项多中心病例对照研究。肺动脉高压患者平均肺动脉压25 mm Hg，肺血管阻力240dynes·S·cm−5，肺动脉楔压≤15 mm Hg，无其他原因引起的肺动脉高压。对照组为晚期肝病患者，超声心动图显示右室(RV)收缩压<40 mm Hg，右室功能正常。我们使用TaqMan技术对CYP19A1和CYP1B1中的三个SNPs进行了基因分型，并使用全基因组标记将SNPs注入了ESR1。检测血液和尿样中的雌激素代谢产物。POPH组37例，对照组290例。平均年龄为57岁，其中36%为女性。CYP19A1的风险等位基因rs7175922与雌二醇水平升高(p=0.02)和POPH风险增加(OR 2.36，95%CI 1.12~4.91，p=0.02)显著相关，而其他SNPs与POPH风险增加无关。高尿2-羟基雌激素/16-α-羟雌酮(2-OHE/16-α-OHE1)(OR=2.04，95%CI 1.16~3.57，P=0.01)，降低血浆硫酸脱氢表雄酮(OR=2.38，95%CI 1.56~3.85，p<；0.001)和较高的血浆16-羟基雌二醇(16-α-α)水平(OR=2.16，95%可信区间1.61~2.98，p<；0.001)。芳香酶的遗传变异和雌激素代谢产物的变化与POPH有关。
Portopulmonary hypertension (POPH) was previously associated with a single nucleotide polymorphism (SNP) rs7175922 in aromatase (CYP19A1). We sought to determine if genetic variants and metabolites in the estrogen signaling pathway are associated with POPH. We performed a multicenter case-control study. POPH patients had mean pulmonary artery pressure > 25 mmHg, pulmonary vascular resistance > 240 dynes•s•cm−5, and pulmonary artery wedge pressure ≤ 15 mmHg without another cause of pulmonary hypertension. Controls had advanced liver disease, right ventricular (RV) systolic pressure < 40 mmHg and normal RV function by echocardiography. We genotyped three SNPs in CYP19A1 and CYP1B1 using TaqMan and imputed SNPs in ESR1 using genome-wide markers. Estrogen metabolites were measured in blood and urine samples. There were 37 patients with POPH and 290 controls. The mean age was 57 years and 36% were female. The risk allele rs7175922 in CYP19A1 was significantly associated with higher levels of estradiol (p = 0.02) and an increased risk of POPH (OR 2.36, 95% CI 1.12–4.91, p = 0.02) whereas other SNPs were not. Higher urinary 2-hydroxyestrogen/16-α-hydroxyestrone (2-OHE/16α-OHE1) (OR per 1 ln increase = 2.04, 95%CI 1.16–3.57, p = 0.01), lower plasma levels of dehydroepiandrosterone-sulfate (DHEA-S) (OR per 1 ln decrease = 2.38, 95%CI 1.56–3.85, p < 0.001) and higher plasma levels of 16-α-hydroxyestradiol (16α-OHE2) (OR per 1 ln increase = 2.16, 95%CI 1.61–2.98, p < 0.001) were associated with POPH. Genetic variation in aromatase and changes in estrogen metabolites were associated with POPH.
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影响因子：
3.6
作者：
de la Roque, Eric Dumas;Quignard, Jean-Francois;Savineau, Jean-Pierre
通讯作者：
Savineau, Jean-Pierre
影响因子：
7.9
作者：
Austin ED;Hamid R;Hemnes AR;Loyd JE;Blackwell T;Yu C;Phillips Iii JA;Gaddipati R;Gladson S;Gu E;West J;Lane KB
通讯作者：
Lane KB
较低的DHEA-S水平可以预测特发性，结缔组织疾病和先天性心脏病相关的肺动脉高压的绝经后妇女的疾病和恶化。
DOI：
10.1183/13993003.00467-2018
发表时间：
2018-06
期刊：
The European respiratory journal
影响因子：
--
作者：
Baird GL;Archer-Chicko C;Barr RG;Bluemke DA;Foderaro AE;Fritz JS;Hill NS;Kawut SM;Klinger JR;Lima JAC;Mullin CJ;Ouyang P;Palevsky HI;Palmisicano AJ;Pinder D;Preston IR;Roberts KE;Smith KA;Walsh T;Whittenhall M;Ventetuolo CE
通讯作者：
Ventetuolo CE
影响因子：
11.2
作者：
Belous, Alexandra R.;Hachey, David L.;Parl, Fritz F.
通讯作者：
Parl, Fritz F.
DOI：
10.1164/rccm.201605-1024oc
发表时间：
2017-02-01
影响因子：
24.7
作者：
Kawut, Steven M.;Archer-Chicko, Christine L.;Ventetuolo, Corey E.
通讯作者：
Ventetuolo, Corey E.