DRD4 uVNTR and TP53 Codon72 Polymorphisms in Schizophrenia (R1) Running Title: TP53 Pro72Arg in schizophrenia

Background: TP53 is a recently be suspected to be involves in neural apoptotic events. Also, TP53 codon72 and long-form variants of DRD4 uVNTR polymorphism are reported to be conferred susceptibility to schizophrenia, respectively. Methods: Nine hundred and thirty-four schizophrenia patients and 433 healthy individuals were recruited, genotyped for TP53 codon72 and DRD4 uVNTR polymorphism by using PCR, PCR-RFLP and direct sequencing. Results: No significant difference was found in both genotype and allele frequency of TP53 codon72 polymorphism between schizophrenia patients and controls. However, long-form alleles (嗢5-repeat) of DRD4 uVNTR polymorphism were more frequent in schizophrenia patients (P = 0.001), which may a risk factor to be associated with enhanced vulnerability to schizophrenia (OR = 3.189, 95% C.I. = 1.535-6.622). In logistic regression, long-from variants did predict schizophrenia after controlling age and gender (P = 0.036, OR = 2.319), but not the genotype CC or GG of TP53 codon72 polymorphism. Conclusions: The long-form variants of DRD4 uVNTR polymorphism associate with schizophrenia, which independent to TP53 codon72 polymorphism. Also, the TP53 codon72 polymorphism is more likely uncorrelated to schizophrenia, if any; the genetic effect is very small. The other SNPs of p53 gene or others apoptosis-related genes need to be explored to clarify their role in synaptic dysfunction involves in pathogenesis of schizophrenia.