Genetic association of the serotonin transporter in pulmonary arterial hypertension

Am J Respir Crit Care Med. 2006 Apr 1;173(7):793-7. doi: 10.1164/rccm.200509-1365OC. Epub 2006 Jan 6.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • DNA / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / metabolism
  • Infant
  • Middle Aged
  • Mutation
  • Polymorphism, Genetic*
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • DNA