Two novel variants in the DOPA decarboxylase gene: association with bipolar affective disorder

TY - JOUR

T1 - Two novel variants in the DOPA decarboxylase gene: association with bipolar affective disorder

AU - Børglum, A D

AU - Bruun, T G

AU - Kjeldsen, T E

AU - Ewald, H

AU - Mors, O

AU - Kirov, G

AU - Russ, C

AU - Freeman, B

AU - Collier, D A

AU - Kruse, T A

PY - 1999

Y1 - 1999

N2 - DOPA decarboxylase (DDC), also known as aromatic L-amino acid decarboxylase (AADC), is an enzyme involved in the synthesis of the important neurotransmitters dopamine, norepinephrine, and serotonin. In addition, it participates in the synthesis of trace amines; compounds suggested to act as endogenous modulators of central neurotransmission. Thus, DDC is regarded as a potential susceptibility gene for a variety of neuropsychiatric disorders. The aim of the present study was to examine the role of DDC in bipolar affective disorder (BPAD). By screening 10 individuals for sequence variations in the coding region of the DDC gene as well as in the neuron-specific promoter and 5' untranslated regions we were able to identify two fairly frequent variants: a 1-bp deletion in the promoter and a 4-bp deletion in the untranslated exon 1. Both deletions affect putative binding sites for known transcription factors, suggesting a possible functional impact at the level of expression. The two variants were applied in an association study including 80 Danish bipolar patients, 112 English bipolar patients, 223 Danish controls, and 349 English controls. Analyzing the combined material, a significant association was found between the 1-bp deletion and BPAD with P-values of 0.037 (allelic) and 0.021 (genotypic). The frequency of the 1-bp deletion was 13.3% in patients and 9.4% in controls with a corresponding odds ratio of 1. 48 (95% CI: 1.02-2.15). The results presented suggest that DDC may act as a minor susceptibility gene for bipolar affective disorder.

AB - DOPA decarboxylase (DDC), also known as aromatic L-amino acid decarboxylase (AADC), is an enzyme involved in the synthesis of the important neurotransmitters dopamine, norepinephrine, and serotonin. In addition, it participates in the synthesis of trace amines; compounds suggested to act as endogenous modulators of central neurotransmission. Thus, DDC is regarded as a potential susceptibility gene for a variety of neuropsychiatric disorders. The aim of the present study was to examine the role of DDC in bipolar affective disorder (BPAD). By screening 10 individuals for sequence variations in the coding region of the DDC gene as well as in the neuron-specific promoter and 5' untranslated regions we were able to identify two fairly frequent variants: a 1-bp deletion in the promoter and a 4-bp deletion in the untranslated exon 1. Both deletions affect putative binding sites for known transcription factors, suggesting a possible functional impact at the level of expression. The two variants were applied in an association study including 80 Danish bipolar patients, 112 English bipolar patients, 223 Danish controls, and 349 English controls. Analyzing the combined material, a significant association was found between the 1-bp deletion and BPAD with P-values of 0.037 (allelic) and 0.021 (genotypic). The frequency of the 1-bp deletion was 13.3% in patients and 9.4% in controls with a corresponding odds ratio of 1. 48 (95% CI: 1.02-2.15). The results presented suggest that DDC may act as a minor susceptibility gene for bipolar affective disorder.

KW - Alleles

KW - Base Sequence

KW - Bipolar Disorder

KW - Brain Chemistry

KW - DNA Mutational Analysis

KW - Denmark

KW - Dopa Decarboxylase

KW - England

KW - Exons

KW - Family Health

KW - Gene Deletion

KW - Genetic Variation

KW - Genotype

KW - Humans

KW - Linkage (Genetics)

M3 - Journal article

C2 - 10578236

SN - 1359-4184

VL - 4

SP - 545

EP - 551

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 6

ER -