RESUMO
Neuroleptic induced akathisia is a common and distressful extrapyramidal side effect of antipsychotic treatment. A significant proportion of the variability of its development has been left unexplained and has to be attributed to individual susceptibility. Since hereditary factors have been discussed in the etiology of acute akathisia (AA), part of the individual susceptibility might be of genetic origin. Moreover, AA is regarded as a forerunner of tardive dyskinesia, a drug-induced chronic movement disorder, which may be associated with homozygosity for the Ser9Gly variant of the DRD3 gene. Considering expression studies, which demonstrated functional variants of DRD3 polymorphisms, we investigated whether homozygosity for the Ser9Gly variant of the DRD3 gene is associated with AA. Homozygosity for the Ser9Gly variant of the DRD3 gene was connected to an 88% incidence of AA as compared with a considerably lower 46.9% incidence of AA in schizophrenic patients nonhomozygous for the 2-2 allele (exact P = 0.0223). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:187-191, 2000.
Assuntos
Acatisia Induzida por Medicamentos/genética , Discinesias/genética , Variação Genética/genética , Receptores de Dopamina D2/genética , Esquizofrenia/genética , Doença Aguda , Acatisia Induzida por Medicamentos/etiologia , Substituição de Aminoácidos , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Discinesias/etiologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Alemanha , Haloperidol/efeitos adversos , Haloperidol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Receptores de Dopamina D3 , Esquizofrenia/tratamento farmacológicoRESUMO
hSKCa3 is a neuronal small conductance calcium-activated potassium channel, which contains a polyglutamine tract, encoded by a polymorphic CAG repeat in the gene. Since an association between longer alleles of this CAG repeat and bipolar disorder or schizophrenia has been reported, we genotyped the polymorphic CAG repeat in 91 German family trios of patients with bipolar disorder I and used the transmission disequilibrium test (TDT) to test for association. Applying a dichotomized model (< or = 19 or > 19 CAG triplets), we found no evidence for an association of longer alleles with bipolar disorder (TDT = 0.75, P = 0.386). Regarding the whole range of alleles, there was no preference in transmitting the larger of the two observed alleles from parents to the affected offspring. In parallel we performed an independent case-control study on German patients with bipolar disorder and schizophrenia. Again we did not detect an overrepresentation of longer CAG repeats in patients. Thus, our data do not support the hypothesis that longer CAG repeats in the hSkCa3 gene contribute to the susceptibility for bipolar disorder and schizophrenia.
Assuntos
Transtorno Bipolar/genética , Neuropeptídeos/genética , Polimorfismo Genético , Canais de Potássio/genética , Esquizofrenia/genética , Repetições de Trinucleotídeos , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Alemanha , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Núcleo Familiar , Valores de Referência , Canais de Potássio Ativados por Cálcio de Condutância BaixaRESUMO
Evidence for the operation of expanded trinucleotide repeats in the pathogenesis of bipolar affected disorder has recently been found at the molecular genetic level. For the screening of these repeat motifs in genomes of patients with bipolar affective disorder, we established a modified PCR-based fingerprinting technique, called triplet repeat enhanced arbitrarily primed PCR (TREAP-PCR). Using this approach, 40 patients suffering from bipolar affective disorder (ICD10: F31) and 15 healthy controls were investigated. Interindividual polymorphisms generated by TREAP-PCR seemed to depend on the type of triplet. Using CCG triplet primers, polymorphisms could be observed more often in the genomes of patients compared with controls, whereas no significant differences could be found using primers of the CAG or AAT type. These data might indicate the existence of subgroups of manic-depressive patients based on molecular genetic differences.
Assuntos
Transtorno Bipolar/genética , Genoma Humano , Repetições de Trinucleotídeos/genética , Adulto , Transtorno Bipolar/patologia , DNA/química , DNA/genética , Impressões Digitais de DNA , Primers do DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Polimorfismo Genético , Análise de Sequência de DNARESUMO
We have cloned and sequenced a wound-inducible cDNA clone designated WIP1 (for wound-induced protein) from maize coleoptiles. It was isolated by differential screening of a cDNA library prepared from excised maize coleoptile segments. The deduced amino acid sequence predicts a secretory, cysteine-rich protein of 102 residues with a calculated molecular mass of 11 kDa and a typical N-terminal signal sequence. The protein has about 30% identity with various Bowman-Birk type proteinase inhibitors. Most interestingly, it is novel in that it is double-headed with exclusive specificity for chymotrypsin. WIP1 is strongly wound-induced in contrast to other members of the Bowman-Birk proteinase inhibitor family, which occur in seeds and are regulated during development. The response is fast, similar to defence-induced genes, and measurable as early as 30 min after wounding. Induction can also be evoked in the intact coleoptiles and the signal is systematically transmitted in the coleoptile to adjacent regions of the wounded area. Isolation and analysis of the corresponding genomic clone reveals that WIP1 contains an intron of 90 nucleotides.