Polymorphisms in the serotonin transporter protein (SERT) gene in patients with pulmonary arterial hypertension

Abstract

Serotonin is a potent vasoconstrictor and pulmonary vascular growth factor whose concentration is increased in patients with pulmonary arterial hypertension (PAH). Its functions are mediated in part by the serotonin transporter protein (SERT) whose gene can have two allelic forms, both long (L) and short (S). The first was associated with greater function.

Objectives: To determine whether the prevalence of the L allelic form of SERT is higher in patients with PAH than in the general population. To observe whether there are any clinical differences in patients with PAH based on the SERT allele.

Methods: We included patients diagnosed with PAH with catheterization based on the established criteria. Peripheral blood samples were taken and the DNA was extracted from the peripheral leukocytes. We amplified the promoter region of SERT by polymerase chain reaction and separated the products by electrophoresis. The patient samples were compared with samples from 50 healthy controls and among the most common types of PAH (idiopathic, thromboembolic and associated with connective tissue disorders). Several clinical variables were assessed according to the SERT gene alleles.

Results: The study included 50 patients, and adequate samples were obtained in 49 (30 women). Mean age at diagnosis was 56 ± 16 years. No differences were seen in the distribution of alleles between patients and controls (P = .54). There were no differences among the three most common types of PAH (P = .3). The most frequent allelic form was LS (54% patients, 56% controls). There were no differences in either age of diagnosis or response to treatment according to the SERT alleles. There was a trend toward higher mean pulmonary pressure levels in the LL forms (49 ± 5 mm Hg vs 42 ± 9 mm Hg, P = .07).

Conclusions: The distribution of SERT gene alleles does not appear to be different in patients with PAH than in the normal population. Different types of PAH have a similar distribution of alleles. The LL forms do not appear to confer either clinical differences or differences in response to treatment.