No Structural Mutation In the Dopamine D: Analysis Using Denaturing Gradient Gel Electrophoresis2: Analysis Using Denaturing Gradient Gel Electrophoresis Receptor Gene In Alcoholism or Schizophrenia: Analysis Using Denaturing Gradient Gel Electrophoresis

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Abstract

OBJECTIVE

To examine the dopamine D2 receptor (DRD2) gene coding sequences for abnormalities associated with schizophrenia or alcoholism and thereby help to resolve the controversy surrounding the reported association of alcoholism with a restriction fragment length polymorphism located close to the DRD2 gene.

DESIGN

Mutational analysis of complete DRD2 gene coding sequences by denaturing gradient gel electrophoresis followed by direct nucleotide sequencing of detected variants.

SETTING

Patients and controls from clinical and epidemiologic collections in the United States and Europe.

PATIENTS

A total of 253 unrelated individuals, including 106 patients with schizophrenia, 113 with alcoholism, and 34 controls. For alcoholism we included patients from previously published series in which an association of illness with allele A1 was reported (Taq I site 3' to the DRD2 gene) and from other published series in which nonconfirmations of this association were reported. Nearly all persons examined were white.

MAIN OUTCOME MEASURES

Frequency of nonsilent variations in DRD2 gene DNA sequences in the different diagnostic groups.

RESULTS

We found three infrequent DNA variants that predict altered amino acid sequence of the receptor. None of these is associated with either alcoholism or schizophrenia.

CONCLUSION

No structural coding abnormalities in the DRD2 gene are present in alcoholism or schizophrenia.

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