RESUMEN
OBJECTIVE: To investigate whether functional polymorphisms directly (HTR2A and SLC6A4 genes) or indirectly (IL-1 gene complex, APOE and ACE genes) related with serotonergic neurotransmission were associated with suicidal behavior. SUBJECTS AND METHODS: 227 suicide attempters, 686 non-suicidal psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS: There were no differences in genotype frequencies between the three groups. The -1438A/G [χ(2) (df)=9.80 (2), uncorrected p=0.007] and IL-1α -889C/T [χ(2) (df)=8.76 (2), uncorrected p=0.013] genotype frequencies between impulsive and planned suicide attempts trended toward being different (not significant after Bonferroni correction). Suicide attempts were more often impulsive in the presence of -1438G/G or IL-1α -889C/T or C/C genotypes. There was interaction between the polymorphism 5-HTTLPR and age [LRT (df)=6.84 (2), p=0.033] and between the polymorphisms APOE and IL-1RA (86bp)(n) [LRT (df)=12.21 (4), p=0.016] in relation to suicide attempt lethality. CONCLUSION: These findings further evidence the complexity of the association between genetics and suicidal behavior, the need to study homogenous forms of the behavior and the relevance of impulsive and aggressive traits as endophenotypes for suicidal behavior.
Asunto(s)
Apolipoproteínas E/genética , Proteína Antagonista del Receptor de Interleucina 1/genética , Interleucina-1/genética , Trastornos Mentales/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Serotonina/genética , Transmisión Sináptica/genética , Adulto , Estudios de Casos y Controles , Endofenotipos , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Predisposición Genética a la Enfermedad/psicología , Genotipo , Humanos , Masculino , Trastornos Mentales/psicología , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Receptor de Serotonina 5-HT2A/genética , Suicidio/psicología , Suicidio/estadística & datos numéricos , Población Blanca/genética , Población Blanca/psicologíaRESUMEN
BACKGROUND: To date, research examining the relationship between serotonergic genes and obsessive-compulsive disorder (OCD) has yielded conflicting results. The purpose of this study is to investigate the association between four serotonergic polymorphisms (STin2 VNTR and 5-HTTLPR of the SLC6A4 gene, and A-1438G (rs6311) and T102C (rs6313) of the HTR2A gene) and OCD. METHODS: 99 OCD patients, 456 non-OCD psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS: All groups showed Hardy-Weinberg equilibrium for the analyzed genetic variability. A-1438G and T102C polymorphisms were in complete linkage disequilibrium. OCD patients showed an excess of STin2.12 carriers (12/12, 12/10, and 12/9 genotypes) compared with healthy controls (chi(2) (1)=7.21, corrected p=0.021; OR=3.38, 95% CI=1.32-8.62) and non-OCD psychiatric patients (chi(2) (1)=6.70, corrected p=0.030; OR=3.24, 95% CI=1.27-8.26). However, no differences were found between non-OCD patients and healthy controls (chi(2) (1)=0.05, corrected p>1; OR=1.04, 95% CI=0.72-1.51). No significant differences were found with respect to A-1438G and 5-HTTLPR polymorphisms. CONCLUSIONS: Our data provide supporting evidence of an association between the STin2 VNTR polymorphism of the SLC6A4 gene and OCD.