Published ahead of print on January 6, 2006, doi:10.1164/rccm.200509-1365OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200509-1365OC
Genetic Association of the Serotonin Transporter in Pulmonary Arterial HypertensionDivision of Medical Genetics, Departments of Genetics and Cardiovascular Sciences, University of Leicester, Leicester; Pulmonary Vascular Diseases Unit, Papworth Hospital National Health Service Trust, Papworth Everard; National Heart and Lung Institute and Section on Clinical Pharmacology, Imperial College London; Departments of Genetics and Molecular Medicine (Guy's Campus), Kings College, London; Department of Clinical Genetics, St. James's University Hospital, Leeds; Respiratory Medicine Unit, Department of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom; Institute of Human Genetics, University of Heidelberg; Department of Cardiology and Pneumology, University Hospital Heidelberg, Heidelberg; Department of Pneumology, Medizinische Hochschule Hannover, Hannover; University Giessen Lung Center, Department of Internal Medicine, Justus-Liebig University, Giessen, Germany; LDS Hospital and University of Utah, Salt Lake City, Utah; and Department of Chest Medicine, National Research Institute of Tuberculosis and Lung Diseases, Warsaw, Poland Correspondence and requests for reprints should be addressed to Richard C. Trembath, M.D., Departments of Genetics and Molecular Medicine (Guy's Campus), Kings College, London SE1 1UL, UK. E-mail: richard.trembath{at}genetics.kcl.ac.uk Rationale: The bone morphogenetic receptor type II gene is the major genetic determinant for the inherited form of pulmonary arterial hypertension. However, deleterious mutations of this gene are not observed in the majority of subjects who develop the condition spontaneously and familial disease displays age- and sex-dependent penetrance, indicating the requirement for additional environmental and/or genetic modifiers for disease development. Methods: We investigated polymorphic variation of the serotonin transporter gene, a biological candidate for predisposition to this vascular disorder. Results: No significant evidence of association between alleles of the serotonin transporter gene and pulmonary hypertension was detected, nor did we observe a relationship with age of onset in familial and idiopathic disease. Conclusions: Variation of the serotonin transporter gene appears unlikely to confer significant susceptibility to pulmonary arterial hypertension. This study emphasizes the need for adequately powered cohorts for association analyses to identify not only genetic determinants of disease susceptibility but also inherited modifiers for disease development.
Key Words: BMPR2 • modifier • penetrance • polymorphism This article has been cited by other articles:
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