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The aim of this study was to investigate the association between the exonic single nucleotide polymorphisms (SNPs) of synapsin I (SYN1) (rs1142636, Asn170Asn, Xp11.23) and SYN2 (rs2289708, 3′-untranslated region, 3p25) in schizopherenia. Methods: Two hundred eighty six schizophrenia patients and 304 control subjects were recruited. SNPs with a know heterozygosity and minor allele frequency (MAF) > 0.1 in Asian populations were selected and genotyped by direct sequencing. Results: The allelic frequencies of rs1142636 (SYN1) were associated with schizophrenia (P < 0.05), respectively. The allelic frequency of rs1142636 in all subjects was associated with schizophrenia [P = 0.000059, OR = 2.17 (95% CI = 1.47–3.18)]. The C allele frequency of rs1142636 was higher in schizophrenia (20.8%) than that in controls (10.8%). In the analysis of gender, the allelic frequency of rs1142636 was also strongly associated with female schizophrenia [P = 0.0001, OR = 2.65 (95% CI = 1.61–4.36)], but not with male schizophrenia. The C allele frequency of rs1142636 was higher in female schizophrenia (22.2%) than that in female controls (9.7%). The rs2289708 SNP (SYN2) did not show any association between schizophrenia and controls. Conclusions: These results suggest that the C allele of a synonymous SNP (rs1142636, Asn170Asn, Xp11.23) in SYN1 may be a risk factor for the susceptibility of Koreran female schizophrenia.