RESUMEN
Several lines of evidence suggest an involvement of the noradrenergic neurotransmitter system in the pathogenesis of bipolar affective disorder (BPAD). Three genes for alpha-adrenergic receptors (ADRA) are located in chromosomal regions that showed evidence for linkage: The alpha(1c)-adrenergic (ADRA-1C) receptor gene on 8p21, the alpha(2a)-adrenergic (ADRA-2A) receptor gene on 10q25, and the alpha(2c)-adrenergic (ADRA-2C) receptor on 4p16. In a BPAD sample of 120 parent-offspring triads, we genotyped a 492 Cys/Arg variant in exon 2 of the ADRA-1C gene, a -1291 G/C variant in the 5'UTR of the ADRA-2A gene, and a STR marker (adra2c1) in the 5'UTR of the ADRA-2C gene. Using the Transmission Disequilibrium Test (TDT), no significant differences in transmissions were observed for any of the three ADRA genes.
Asunto(s)
Trastorno Bipolar/genética , Cromosomas Humanos Par 10/genética , Cromosomas Humanos Par 8/genética , Variación Genética/genética , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 2/genética , Regiones no Traducidas 5'/genética , Niño , Transmisión de Enfermedad Infecciosa , Familia , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Desequilibrio de Ligamiento , MasculinoRESUMEN
We have investigated the gene for dystrobrevin-binding protein 1 (DTNBP1), or dysbindin, which has been strongly suggested as a positional candidate gene for schizophrenia, in three samples of subjects with schizophrenia and unaffected control subjects of German (418 cases, 285 controls), Polish (294 cases, 113 controls), and Swedish (142 cases, 272 controls) descent. We analyzed five single-nucleotide polymorphisms (P1635, P1325, P1320, P1757, and P1578) and identified significant evidence of association in the Swedish sample but not in those from Germany or Poland. The results in the Swedish sample became even more significant after a separate analysis of those cases with a positive family history of schizophrenia, in whom the five-marker haplotype A-C-A-T-T showed a P value of.00009 (3.1% in controls, 17.8% in cases; OR 6.75; P=.00153 after Bonferroni correction). Our results suggest that genetic variation in the dysbindin gene is particularly involved in the development of schizophrenia in cases with a familial loading of the disease. This would also explain the difficulty of replicating this association in consecutively ascertained case-control samples, which usually comprise only a small proportion of subjects with a family history of disease.
Asunto(s)
Proteínas Portadoras/genética , Esquizofrenia/genética , Disbindina , Proteínas Asociadas a la Distrofina , Frecuencia de los Genes , Haplotipos/genética , Humanos , Polimorfismo de Nucleótido Simple/genética , Población BlancaRESUMEN
A duplication of chromosome 15q24-q26 (DUP25) has been reported to be associated with anxiety disorders. We tested for the presence of DUP25 in a sample of 50 patients with panic disorder and 50 controls using a quantitative real-time PCR approach. Contrary to the original finding, our results were compatible with the absence of DUP25, and no significant difference could be detected between patients and controls ( P=1.0). Thus, our study does not support the hypothesis of an involvement of DUP25 in panic disorder.