Plasma levels of S100A4 in portopulmonary hypertension

Abstract

We previously showed that a single nucleotide polymorphism in S100A4 was associated with portopulmonary hypertension (PPHTN) in patients with advanced liver disease. We aimed to determine the association between plasma levels of S100A4 and PPHTN. We performed a case–control study of patients with advanced liver disease. Cases with PPHTN had mean pulmonary artery pressure >25 mmHg, pulmonary vascular resistance >240 dynes s cm⁻⁵ and pulmonary capillary wedge pressure ≤15 mmHg. Controls with liver disease had right ventricular systolic pressure <40 mmHg and normal right atrial and ventricular morphology by echocardiography. Plasma samples were assayed for S100A4. The study sample included 14 cases with PPHTN and 32 controls with liver disease. There was no difference in mean age between cases and controls (p = 0.52). Seventy-nine percent of cases were female compared with 44% of controls (p = 0.03). There was no difference in S100A4 levels between cases and controls (p = 0.58). Both groups had significantly higher S100A4 levels than healthy volunteers (p <0.05). There was no significant difference in plasma levels of S100A4 between PPHTN patients and controls with liver disease, although liver disease itself was associated with increased S100A4 levels.

Keywords::

• Portal hypertension
• pulmonary arterial hypertension
• genetic susceptibility
• S100A4

Acknowledgements

We thank Charles A. Powell, May Huang, John O’Connor and the other staff at the Irving Institute for Clinical and Translational Research for their assistance. The study was funded by NIH grants DK064103, DK065958, RR00645, RR00585, RR00046, RR00032, RR024156 and HL67771.

Declaration of interest: S.M.K. has received lecture fees, consultancy fees and/or other support from Actelion, Pfizer, Gilead, Lilly, Novartis, INO Therapeutics, United Therapeutics, Gerson Lehrman and Clinical Advisors. M.J.K. has provided consultation regarding possible clinical trials concerning portopulmonary hypertension for Gilead, United Therapeutics and Actelion. The other authors have not declared a potential conflict of interest.

The pulmonary vascular complications of liver disease study group

The Pulmonary Vascular Complications of Liver Disease Study Group also includes: Columbia University: Jeffrey Okun, Daniel Rabinowitz, Evelyn M. Horn, Lori Rosenthal, Sonja Olsen, Jenna Reinen; Mayo Clinic: Vijay Shah, Russell Wiesner, Linda Stadheim; University of Alabama: J. Stevenson Bynon, Devin Eckhoff, Harpreet Singh, Rajasekhar Tanikella, Keith Wille, Dorothy Faulk; University of Colorado: Lisa Forman, David Badesch, Ted Perry; The University of North Carolina at Chapel Hill: Roshan Shrestha, Carrie Nielsen, Steven Zacks; University of Pennsylvania: Vivek Ahya, Harold Palevsky, Rajender Reddy, Michael Harhay, Sandra Kaplan; University of Southern California: Neil Kaplowitz, James Knowles.