摘要:

Given the efficacy of medications that interact with the serotonin transporter (5-HTT) in the treatment of panic disorder, we have used a family-based design to test for genetic association and linkage between panic disorder and a functional polymorphism in the promoter of the gene for 5-HTT. In this study, 340 individuals in 45 families, as well as 74 haplotype relative risk ‘trios’ were genotyped at the polymorphic locus, which consists of a 44 base pair deletion/insertion. There were no significant differences in allele frequencies or occurrence of genotypes within the triads. No linkage between the 5-HTT polymorphism and panic disorder was observed in the multiplex families, using a variety of simulations for dominant and recessive models of inheritance. Recent reports suggest an association between the 5-HTT polymorphism and anxiety-related traits, as measured with personality assessment. The results reported here provide evidence that the genetic basis of panic disorder may be distinct from anxiety-related traits assessed by personality inventories in normal populations. © 1999 Lippincott Williams & Wilkins.

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The gene for spinocerebellar ataxia type 1 (SCA1) is a potential candidate gene for schizophrenia because of previous positive linkage findings in this region (6p22–24), and because the reported correlation between SCA1 onset and the number of CAG repeats suggests anticipation. To test the involvement of this gene in the development of schizophrenia, we examined genotypes of the SCA1 CAG repeat polymorphism for 49 Caucasian patients with schizophrenia, and 88 Caucasian controls. We found a significant association between the frequencies of alleles of this gene and schizophrenia (X2= 18.40, df = 8,P= 0.018). Among 13 alleles, one alleie (31 trinucleotide repeat) was significantly more frequent in patients with schizophrenia than in controls (X2= 957, df = 1,P= 0.002). This association was sustained after applying a Bonferroni correction for multiple testing (P= 0.05/13 = 0.004), and the chi-square results were shown to be robust through Monte Carlo simulation. We observed no allelic association with three flanking microsatellite markers (D6S288, D6S1605, and D6S337), suggesting that our result was not due to population stratification. Further studies of this locus are needed to confirm this finding, and to determine a potential role for this gene in the development of schizophrenia. © 1999 Lippincott Williams & Wilkins.

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

A number of association studies have investigated the role of the monoamine oxidase A (MAOA) gene in the susceptibility to bipolar disorder. Although some studies have reported positive findings, there remains some controversy, because results from different studies have not been consistent. A common explanation for inconsistencies between studies is genetic heterogeneity. We have focused on lithium responsive bipolar disorder as a way to reduce heterogeneity. In this study, we investigated the role of MAOA in lithium responsive bipolar patients using association and linkage study designs. The investigation used 138 patients and 108 normal controls. In addition, 25 families were also studied. Our results were not supportive of a major role of MAOA in the predisposition to bipolar disorder. © 1999 Lippincott Williams & Wilkins.

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Hereditary dopaminergic mechanisms have been implicated in the aetiology of alcoholism. For this study, the distribution of a dopamine D3 receptor gene polymorphism (Ball) has been investigated in patients suffering from alcohol dependence, and compared with non-dependent controls. The allele A1 occurred significantly more frequently among patients compared to controls. Patients with the genotype A1/A2 showed significantly higher novelty seeking (NS) scores in the tridimensional personality questionnaire (TPQ) than patients with the genotype A1/A1. The distribution of patients with high and low NS scores in heterozygotes (A1/A2) did not follow a random distribution. There were significantly more individuals with higher NS scores, and fewer individuals with lower NS scores than expected. The results of this study support the hypothesis of a genetically determined involvement of the dopaminergic system in alcohol dependence. This is probably related to the modulation of personality traits. The observed effects are relatively small, but statistically significant. Thus, the genetics of the dopaminergic neurotransmitter system alone cannot explain the aetiopathogenesis of alcoholism. © 1999 Lippincott Williams & Wilkins.

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The Faroe Islands are a small group of islands in the North Atlantic Ocean, situated between Norway, Iceland and Scotland. The origin of the population is thought to be a mixture of Norwegian, Danish and British. The islands were populated at the same time as Iceland, i.e. around 1100 years ago, and the size of the population was around, and occasionally below, 4000 inhabitants until 1800, after which it increased to its present-day level of around 45000. The population is descended from Scandinavian and British ancestors. Because of the low number of founders and small size for many centuries, the Faroese population is perhaps the most valuable European population for genetic mapping of complex disease genes.The present study searched for haplotype sharing on chromosome 18 among eight lithium responding patients with bipolar affective disorder related, on average, 6.2 generations ago, using 30 DNA markers. In order to obtain as homogeneous a sample as possible, strict inclusion criteria based on severity of phenotype, geography and treatment response, were applied.Evidence suggestive of increased haplotype sharing on the distal part of chromosome 18q23 in the region implicated by Freimer and co-workers was found. However, methods of genetic analysis which might provide a conclusive result are not yet available. © 1999 Lippincott Williams & Wilkins.

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Microtubule-associated protein-2 (MAP-2) expression is altered in response to a number of physiological insults such as Alzheimer's disease, schizophrenia, stroke and AIDS-dementia. Changes include alteration in MAP-2 transcription, translation, and state of phosphorylation. Multiple MAP-2 transcripts exist within the nervous system and, as noted for a number of genes expressed in the central nervous system, MAP-2 contains a region of trinucleotide repeats located in exon 1 of the 5′ untranslated region (5′ UTR). Since expansion of CAG repeats are found in several neurodegenerative disorders, we analysed the CAG repeats in MAP-2 for polymorphisms in 31 controls, 35 chronic schizophrenics, and 20 with other neuropsychiatric illnesses. Genomic DNA samples from 86 individuals were used as templates in PCR amplifications with primers within exon 1. Sequencing of the PCR products, or short tandem repeat polymorphism (STRP) analysis, demonstrated consistency in the size of the CAG repeats. This study demonstrates that the seven copies of the CAG repeat located in the 5′ UTR of the MAP-2 gene are highly conserved in the general population, and that there is no evidence for expansion of the CAG repeat. © 1999 Lippincott Williams & Wilkins.

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0955-8829    

出版商:OVID    

年代:1999

数据来源: OVID