Genetic Association of the Serotonin Transporter in Pulmonary Arterial Hypertension

• Published in: American journal of respiratory and critical care medicine 2006-04, Vol.173 (7), p.793-797
• Main Authors: Machado, Rajiv D, Koehler, Rolf, Glissmeyer, Eric, Veal, Colin, Suntharalingam, Jay, Kim, Miryoung, Carlquist, John, Town, Margaret, Elliott, C. Gregory, Hoeper, Marius, Fijalkowska, Anna, Kurzyna, Marcin, Thomson, Jennifer R, Gibbs, Simon R, Wilkins, Martin R, Seeger, Werner, Morrell, Nicholas W, Gruenig, Ekkehard, Trembath, Richard C, Janssen, Bart
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Child; Child, Preschool; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; DNA - genetics; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Hypertension, Pulmonary - genetics; Hypertension, Pulmonary - metabolism; Infant; Intensive care medicine; Medical sciences; Middle Aged; Mutation; Pneumology; Polymorphism, Genetic; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Serotonin Plasma Membrane Transport Proteins - genetics
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200509-1365OC

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. We investigated polymorphic variation of the serotonin transporter gene, a biological candidate for predisposition to this vascular disorder. 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. 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.