Schizophrenia is a common neuropsychiatric disorder with complex pathophysiology. Recent reports suggested that complement system alterations contributed to pathological synapse elimination that was associated with psychiatric symptoms in schizophrenia. Complement component 3 (C3) and complement component 4 (C4) play central roles in complement cascades. In this study, we compared peripheral C3 and C4 protein levels between first-episode psychosis (FEP) and healthy control (HC). Then we explored whether single nucleotide polymorphisms (SNPs) at C3 or C4 genes affect peripheral C3 or C4 protein levels. In total, 181 FEPs and 204 HCs were recruited after providing written informed consent. We measured serum C3 and C4 protein levels using turbidimetric inhibition immunoassay and genotyped C3 and C4 polymorphisms using the Sequenom MassArray genotyping. Our results showed that three SNPs were nominally associated with schizophrenia (rs11569562/C3: A > G, p = 0.048; rs2277983/C3: A > G, p = 0.040; rs149898426/C4: G > A, p = 0.012); one haplotype was nominally associated with schizophrenia, constructed by rs11569562–rs2277983–rs1389623 (GGG, p = 0.048); FEP had higher serum C3 and C4 (both p < 0.001) levels than HC; rs1389623 polymorphisms were associated with elevated C3 levels in our meta-analysis (standard mean difference, 0.50; 95% confidence interval, 0.30 to 0.71); the FEP with CG genotype of rs149898426 had higher C4 levels than that with GG genotypes (p = 0.005). Overall, these findings indicated that complement system altered in FEP and rs149898426 of C4 gene represented a genetic risk marker for schizophrenia likely through mediating complement system. Further studies with larger sample sizes needs to be validated.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may manifest as neonatal hyperbilirubinemia, is the most prevalent erythrocytic enzyme-related disease in the world.Objective: To investigate the association between neonatal hyperbilirubinemia and co-inheritance of G6PD deficiency and 211 G to A variation of UGT1A1 in Chaozhou city of eastern Guangdong province, the effects of G6PD deficiency and UGT1A1 gene variant on the bilirubin level were determined in neonates with hyperbilirubinemia.Method: The activity of G6PD was assayed by an auto-bioanalyzer. PCR and flow-through hybridization were used to detect 14 common G6PD mutations in G6PD deficient neonates. 211 G to A variation of UGT1A1 was determined by PCR and sequencing. The data of neonatal peak bilirubin was collected and analyzed retrospectively.Results: 74 cases of the 882 hyperbilirubinemia neonates were G6PD deficiency (8.39%) while 12 cases of the 585 non-hyperbilirubinemia neonates (control group) were G6PD deficiency (2.05%). The rate of G6PD deficiency in the hyperbilirubinemia group was higher than that of the control group. Moreover, the peak bilirubin in the G6PD-deficient group of hyperbilirubinemia neonates was 334.43±79.27μmol/L, higher than that of the normal G6PD group of hyperbilirubinemia neonates (300.30±68.62 μmol/L). The most common genotypes of G6PD deficiency were c.1376G>T and c.1388G>A, and the peak bilirubin of neonates with these two variants were 312.60±71.81μmol/L and 367.88±75.79 μmol/L, respectively. The bilirubin level of c.1388G>A was significantly higher than that of c.1376G>T. Among the 74 hyperbilirubinemia neonates with G6PD deficiency, 6 cases were 211 G to A homozygous mutation (bilirubin levels 369.55±84.51 μmol/L), 27 cases were 211 G to A heterozygous mutation (bilirubin levels 341.50±63.21 μmol/L), and 41 cases were wild genotypes (bilirubin levels 324.63±57.52 μmol/L). Conclusion: The rate of G6PD deficiency in hyperbilirubinemia neonates was significantly higher than that of the non-hyperbilirubinemia neonates in Chaozhou. For the hyperbilirubinemia group, neonates with G6PD deficiency had a higher bilirubin level compared to those with normal G6PD. For hyperbilirubinemia neonates with G6PD deficiency, there was a declining trend of bilirubin levels among 211 G to A homozygous mutation, heterozygous mutation, and wild genotype, but there was no significance statistically among the three groups.