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Background  The expression of μ-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of μ-opioid receptor gene (OPRM1) with SZ were inconsistent.    Methods  We conducted a case–control study to investigate the genetic association between OPRM1 polymorphisms and SZ among the Han chinese population. 264 SZ patients and 264 age-matched control subjects were recruited. Four SNPs of OPRM1 were successfully genotyped by using PCR-RFLP.    Results  Of four polymorphisms, rs1799971 and rs2075572 were shown to associate with SZ. Compared with the A allele of rs1799971 and C allele of rs2075572, the G allele of rs1799971 and rs2075572 was associated with an almost 0.46-fold risk (OR = 0.46, 95% CI: 0.357-0.59, P < 0.01) and 0.7-fold risk (OR = 0.707, 95% CI: 0.534-0.937, P = 0.015) of the occurrence of SZ,. When subjects were divided by gender, rs1799971 remained significant difference only in males (OR = 0.309, 95% CI: 0.218-0.439 for G allele, P < 0.01), and rs2075572 only in females (OR = 0.399, 95% CI: 0.246-0.648 for G allele, P < 0.01). In secondary analysis with subsets of patients, the G allele of rs1799971 (compared to the A allele) was associated with a decreased risk of all patients and male patients with apathy symptoms (OR = 0.086, 95% CI: 0.048-0.151, P = 0.01; OR = 0.083, 95% CI: 0.045-0.153, P < 0.01), and the G allele of rs2075572 (compared to the C allele) was associated with a decreased risk of all patients and female patients with positive family history (OR = 0.468, 95% CI: 0.309-0.71, P < 0.01; OR = 0.34, 95% CI: 0.195-0.593, P < 0.01). In addition, haplotype analysis revealed that two SNP haplotypes (A-C-C-G and G-C-C-A) were associated with decreased risks of SZ (P < 0.01). The other two (G-C-C-G and G-G-C-G) with increased risks of SZ (P < 0.01).    Conclusions  The present study demonstrated for the first time that the OPRM1 polymorphism may be a risk factor for schizophrenia in the Han Chinese. Further studies are needed to give a global view of this polymorphism in pathogenesis of schizophrenia in a large-scale sample, family-based association design or well-defined subgroups of schizophrenia.

Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population