Association between A-1438G polymorphism in the 2A (5-HT2A) serotonin receptor gene and impulsivity in suicidal behaviour

Paredes B, Alejandra Sáiz P, García-Portilla MP, Morales B, Pajín M, Fernández Hurtado I, García De Eulate I, Álvarez V, Coto E, Bascarán MT, Bousoño M, Bobes J

Objective: To determine the association between four serotonergic polymorphisms (A-

1438G (rs6311) and T102C (rs6313) of the 5-HT2A receptor gene, and STin2 VNTR

and 5-HTTLPR of the SLC6A4 gene) and impulsivity in suicide attempts (SA).

Methods: 180 suicide attempters from Asturias (Northern Spain) were assessed using

the Suicidal Intent Scale (SIS) and genotyped by standard methods. According to the

SIS definition SA were divided into two subgroups (impulsive and non-impulsive). A

score of 6 on the planning subscale was used to classify attempts as impulsive or nonimpulsive.

Results: Mean age (SD) was 35.6 (12.5) years and about 63.3% of cases were female.

Most of patients (95.6%) had at least one psychiatric diagnosis. More prevalent diagnoses

were affective disorders (36.7%), schizophrenia and other psychosis (18.3%), anxiety

disorders (12.2%), and personality disorders (11.1%). Previous SA was found in

49.4% of cases. About 64.4% of SA patients were classified as impulsive SA. A-1438G

and T102C polymorphisms were in complete linkage disequilibrium in our population.

We found and excess of –1438GG genotype and –1438G allele when compared impulsive

SA with the non-impulsive group (34.5% vs 14.1%, ÷2 (2) = 11.5, corrected

P = 0.012; 0.59% vs 0.41%, ÷2 (1) = 11.2, corrected P = 0.004, OR = 2.11 (1.36-3.27),

respectively). No differences in genotypic or allele frequencies of the SLC6A4 gene

polymorphisms were found.

Conclusions: Our findings suggest that polymorphic variants on the 5-HT2A gene may

predispose for impulsive suicidal behaviour.

Alejandra Sáiz P, Bascarán MT, Bobes J, Bousoño M, Coto E, Fernández Hurtado I, García De Eulate I, García-Portilla MP, Morales B, Pajín M, Paredes B, Álvarez V