Dopa decarboxylase genotypes may influence age at onset of schizophrenia

TY - JOUR

T1 - Dopa decarboxylase genotypes may influence age at onset of schizophrenia

AU - Børglum, A D

AU - Hampson, M

AU - Kjeldsen, T E

AU - Muir, W

AU - Murray, V

AU - Ewald, H

AU - Mors, O

AU - Blackwood, D

AU - Kruse, T A

PY - 2001

Y1 - 2001

N2 - Several lines of evidence implicate dopa decarboxylase (DDC) with schizophrenia. By analysis of two putative functional DDC variants in 173 schizophrenic patients and 204 controls we tested the hypotheses that DDC is involved in: (1) predisposition to schizophrenia; and (2) modulation of age at disease onset. No association was observed with schizophrenia as a whole, whereas an association between DDC genotypes and age at disease onset was suggested in males (P = 0.03). This association was most pronounced in relation to genotypes of haplotypes comprising both variants, suggesting an additive model where one variant mediates early and the other late onset. Accordingly, the haplotype-based genotypes could be assigned into three groups by their possible relative effect on age at onset: an "early", "neutral" and "late" group. Dividing the male schizophrenics into four groups with increasing age at onset, the "early" genotypes were seen to decrease in frequency from 51.5% to 16.7% while the "late" genotypes increased from 12.1% to 33.3% (P = 0.02). The difference in mean age at onset between male patients with "early" genotypes vs patients with "late" genotypes was close to 5 years (95% CI: 0.7-8.8). Thus, DDC may possibly act as a modulator of age at onset in male schizophrenics.

AB - Several lines of evidence implicate dopa decarboxylase (DDC) with schizophrenia. By analysis of two putative functional DDC variants in 173 schizophrenic patients and 204 controls we tested the hypotheses that DDC is involved in: (1) predisposition to schizophrenia; and (2) modulation of age at disease onset. No association was observed with schizophrenia as a whole, whereas an association between DDC genotypes and age at disease onset was suggested in males (P = 0.03). This association was most pronounced in relation to genotypes of haplotypes comprising both variants, suggesting an additive model where one variant mediates early and the other late onset. Accordingly, the haplotype-based genotypes could be assigned into three groups by their possible relative effect on age at onset: an "early", "neutral" and "late" group. Dividing the male schizophrenics into four groups with increasing age at onset, the "early" genotypes were seen to decrease in frequency from 51.5% to 16.7% while the "late" genotypes increased from 12.1% to 33.3% (P = 0.02). The difference in mean age at onset between male patients with "early" genotypes vs patients with "late" genotypes was close to 5 years (95% CI: 0.7-8.8). Thus, DDC may possibly act as a modulator of age at onset in male schizophrenics.

KW - Adult

KW - Age of Onset

KW - Brain

KW - Dopa Decarboxylase

KW - Female

KW - Genetic Predisposition to Disease

KW - Haplotypes

KW - Humans

KW - Male

KW - Schizophrenia

U2 - 10.1038/sj.mp.4000902

DO - 10.1038/sj.mp.4000902

M3 - Journal article

C2 - 11673800

SN - 1359-4184

VL - 6

SP - 712

EP - 717

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 6

ER -