RESUMEN
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.
Asunto(s)
Predisposición Genética a la Enfermedad , Trastorno Obsesivo Compulsivo/genética , Polimorfismo Genético/genética , Receptor de Serotonina 5-HT2A/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adulto , Distribución de Chi-Cuadrado , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Twin studies suggest that genetic factors account for 40-60% of the variance in alcohol dependence. It has been stated that different drug dependencies may have unique genetic influences. Alterations in serotonin availability and function can affect drinking behaviour. This study aimed to investigate whether three serotonergic polymorphisms (HTR2A A-1438G (rs6311), and SCL6A4 5-HTTLPR and STin2 VNTR) were associated with alcohol dependence, and, whether the serotonergic polymorphisms played a similar role in conferring vulnerability in alcohol and heroin dependence. METHODS: 165 alcohol dependent patients, 113 heroin dependent patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS: Genotypic frequencies of the A-1438G, 5-HTTLPR, and STin2 VNTR polymorphisms did not differ significantly across the three groups. None of the three polymorphisms contributed to distinguishing alcoholic patients from healthy controls. There was an excess of -1438G and 5-HTTLPR L carriers in alcoholic patients in comparison to the heroin dependent group (OR (95% CI)=1.98 (1.13-3.45) and 1.92 (1.07-3.44), respectively). The A-1438G and 5-HTTLPR polymorphisms also interacted in distinguishing alcohol from heroin dependent patients (Wald (df)=10.21 (4), p=0.037). The association of -1438A/G with alcohol dependence was especially pronounced in the presence of 5-HTTLPR S/S, less evident with 5-HTTLPR L/S and not present with 5-HTTLPR L/L. SCL6A4 polymorphism haplotypes were similarly distributed in all three groups. CONCLUSIONS: Our data do not support a role of serotonergic polymorphisms in alcohol dependence but suggest a differential genetic background to alcohol and heroin dependence.