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

被引:39
作者
Borglum, AD
Bruun, TG
Kjeldsen, TE
Ewald, H
Mors, O
Kirov, G
Russ, C
Freeman, B
Collier, DA
Kruse, TA
机构
[1] Aarhus Univ, Inst Human Genet, DK-8000 Aarhus C, Denmark
[2] Aarhus Univ, Danish Ctr Human Genome Res, Aarhus, Denmark
[3] Hosp Psychiat, Dept A, Mood Disorders Res Unit, Aarhus, Denmark
[4] Hosp Psychiat, Inst Basic Psychiat Res, Dept Psychiat Demog, Aarhus, Denmark
[5] Hosp Psychiat, Inst Basic Psychiat Res, Dept Biol Psychiat, Aarhus, Denmark
[6] Cardiff Univ, Dept Psychol Med, Cardiff CF4 4XN, S Glam, Wales
[7] Inst Psychiat, Dept Neurosci, London SE5 8AF, England
[8] Inst Psychiat, Dept Psychol Med, London SE5 8AF, England
[9] Odense Univ Hosp, KKA, Dept Clin Biochem & Genet, DK-5000 Odense, Denmark
关键词
DDC; AADC; BPAD; gene variants; complex disorder;
D O I
10.1038/sj.mp.4000559
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 l-bp deletion and BPAD with P-values of 0.037 (allelic) and 0.021 (genotypic). The frequency of the l-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.
引用
收藏
页码:545 / 551
页数:7
相关论文
共 55 条
[1]  
*AM PSYCH ASS CON, 1994, DIAGN STAT MAN MENT
[2]   Association between the tryptophan hydroxylase gene and manic-depressive illness [J].
Bellivier, F ;
Leboyer, M ;
Courtet, P ;
Buresi, C ;
Beaufils, B ;
Samolyk, D ;
Allilaire, JF ;
Feingold, J ;
Mallet, J ;
Malafosse, A .
ARCHIVES OF GENERAL PSYCHIATRY, 1998, 55 (01) :33-37
[3]   Aromatic L-amino acid decarboxylase: A neglected and misunderstood enzyme [J].
Berry, MD ;
Juorio, AV ;
Li, XM ;
Boulton, AA .
NEUROCHEMICAL RESEARCH, 1996, 21 (09) :1075-1087
[4]   DANISH TWIN STUDY OF MANIC-DEPRESSIVE DISORDERS [J].
BERTELSEN, A ;
HARVALD, B ;
HAUGE, M .
BRITISH JOURNAL OF PSYCHIATRY, 1977, 130 (APR) :330-351
[5]  
BOULTON AA, 1976, TRACE AMINES BRAIN, P21
[6]  
Bowsher R., 1986, NEUROMETHODS, P33
[7]   MULTIPLE PROMOTERS OF HUMAN CHOLINE-ACETYLTRANSFERASE AND AROMATIC L-AMINO-ACID DECARBOXYLASE GENES [J].
CHIREUX, M ;
RAYNAL, JF ;
LEVANTHAI, A ;
CADAS, H ;
BERNARD, C ;
MARTINOU, JC ;
WEBER, MJ .
JOURNAL OF PHYSIOLOGY-PARIS, 1994, 88 (04) :215-227
[8]   IDENTITY OF DOPA DECARBOXYLASE AND 5-HYDROXYTRYPTOPHAN DECARBOXYLASE [J].
CHRISTENSON, JG ;
DAIRMAN, W ;
UDENFRIEND, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1972, 69 (02) :343-+
[9]   The serotonin transporter is a potential susceptibility factor for bipolar affective disorder [J].
Collier, DA ;
Arranz, MJ ;
Sham, P ;
Battersby, S ;
Vallada, H ;
Gill, P ;
Aitchison, KJ ;
Sodhi, M ;
Li, T ;
Roberts, GW ;
Smith, B ;
Morton, J ;
Murray, RM ;
Smith, D ;
Kirov, G .
NEUROREPORT, 1996, 7 (10) :1675-1679
[10]   LOCALIZATION OF THE GENE FOR HUMAN AROMATIC L-AMINO-ACID DECARBOXYLASE (DDC) TO CHROMOSOME 7P13-]P11 BY INSITU HYBRIDIZATION [J].
CRAIG, SP ;
LEVANTHAI, A ;
WEBER, M ;
CRAIG, IW .
CYTOGENETICS AND CELL GENETICS, 1992, 61 (02) :114-116