RESUMEN
The decrease of glutamic acid decarboxylase (GAD) has been reported as an important neurochemical alteration of the inhibitory GABAergic interneurons in schizophrenia. To our knowledge no studies have investigated the genetic variants influencing GAD expression. To search for markers contributing to the genetic susceptibility of schizophrenia, we typed two polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in both GAD1 and GAD2 genes in 112 triad families and 46 case-controls. We used the Transmission Disequilibrium Test to perform the qualitative family-based analyses and found negative results (GAD1, chi2 = 0.273, 1 degree of freedom, P = 0.60; GAD2, chi2 = 0, 1 degree of freedom, P = 1). In addition there were no associations with GAD1 and GAD2 and quantitative measures of suicide behaviour in this sample. Although our results are negative, this was the first study to investigate GAD genes in schizophrenia, and further studies of these genes, particularly with schizophrenia subtypes, may prove valuable.
Asunto(s)
Glutamato Descarboxilasa/genética , Isoenzimas/genética , Polimorfismo Genético , Esquizofrenia/genética , Edad de Inicio , Alelos , Sustitución de Aminoácidos , Estudios de Casos y Controles , Desoxirribonucleasas de Localización Especificada Tipo II , Femenino , Predisposición Genética a la Enfermedad , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Esquizofrenia/clasificación , Esquizofrenia/epidemiología , SuicidioRESUMEN
Schizophrenia (SCZ) is a severe neuropsychiatric disorder with a strong genetic basis. We analyzed eight GABRG2 and one DRD5 tag single-nucleotide polymorphisms for association with SCZ in 109 small nuclear families and 229 independent SCZ case-control pairs. The marker rs183294 in the 5' region of GABRG2 was found to be associated with SCZ in both samples with the C allele over-represented in SCZ cases and over-transmitted in SCZ families (combined z=9.18; p<1 x 10(-3)). Taken together, the results of the present study suggest that GABRG2 may be involved in SCZ susceptibility, but further studies are required.
Asunto(s)
Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Receptores de GABA-A/genética , Esquizofrenia/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Proteínas Serina-Treonina Quinasas/genética , Adulto JovenRESUMEN
Most antipsychotic drugs act on the forebrain by blocking dopamine receptors. In rodents, the M5 muscarinic receptor (CHRM5) is important for prolonged dopamine release. We typed polymorphisms in CHRM5 and alpha7-nicotinic receptor (CHRNA7) genes on 15q13 in 82 Canadian families having at least 1 schizophrenic patient. Using the Family-Based Association Test, we performed haplotype analysis of the 2 loci and found biased transmission in schizophrenia (z = -2.651, p = 0.008). In the families tested, the 2 cholinergic genes interacted to affect schizophrenia in combination, while neither was sufficiently alone to confer susceptibility. Our present study provided the first line of direct evidence suggesting that the CHRM5 gene combined with the CHRNA7 gene may be linked to schizophrenia.