Association of DRD4 uVNTR and TP53 codon 72 polymorphisms with schizophrenia: a case-control study.
BACKGROUND
The tumour supressor gene TP53 is thought to be involved in neural apoptosis. The polymorphism at codon 72 in TP53 and the long form variants of the upstream variable number of tandem repeats (uVNTR) polymorphism in the dopamine D4 receptor (DRD4) gene are reported to confer susceptibility to schizophrenia.


METHODS
We recruited 934 patients with schizophrenia and 433 healthy individuals, and genotyped the locus of the TP53 codon 72 and DRD4 uVNTR polymorphisms by combining the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) with direct sequencing.


RESULTS
No significant differences were found in the frequency of the genotype of the TP53 codon72 polymorphism between patients with schizophrenia and their controls. However, the long form alleles (> or = 5 repeats) of the DRD4 uVNTR polymorphism were more frequent in patients with schizophrenia than in controls (p = 0.001). Hence, this class of alleles might be a risk factor for enhanced vulnerability to schizophrenia (odds ratio = 3.189, 95% confidence interval = 1.535-6.622). In the logistic regression analysis, the long form variants of the DRD4 polymorphism did predict schizophrenia after the contributions of the age and gender of the subjects were included (p = 0.036, OR = 2.319), but the CC and GG genotypes of the codon 72 polymorphism of TP53 did not.


CONCLUSIONS
The long form variants of the uVNTR polymorphism in DRD4 were associated with schizophrenia, in a manner that was independent of the TP53 codon 72 polymorphism. In addition, given that the genetic effect of the TP53 codon 72 polymorphism on the risk of developing schizophrenia was very small, this polymorphism is unlikely to be associated with schizophrenia. The roles that other single nucleotide polymorphisms (SNPs) in the TP53 gene or in other apoptosis-related genes play in the synaptic dysfunction involved in the pathogenesis of schizophrenia should be investigated.
Lung
For-Wey
FW
Department of Psychiatry, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan. forwey@seed.net.tw
Shu
Bih-Ching
BC
Kao
Wei-Tsung
WT
Chen
C Nathan
CN
Ku
Yu-Chi
YC
Tzeng
Dong-Sheng
DS
D000328:Adult; D016022:Case-Control Studies; D003062:Codon; D005260:Female; D016158:Genes, p53; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D018598:Minisatellite Repeats; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; C493599:DRD4 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050638:Receptors, Dopamine D4