OBJECTIVETo investigate the association of the Neuregulin 1(NRG1) gene polymorphism with schizophrenia by analyzing allele transmission in schizophrenic parent-proband trios.

METHODSQuantitative real-time PCR was used to check the genotypes of four SNPs-rs221533(C/T), rs7820838(C/T), 433E1006(A/G) and rs3924999(C/T), located at the 5o terminus of the Nrg1 gene, in 258 Chinese Han schizophrenic parent-proband trios. The transmission disequilibrium test (TDT) program (Genehunter software 2.0) was used to evaluate the association of the NRG1 gene with schizophrenia.

RESULTSFor all the subjects, the genotypes of the 4 SNPs were in Hardy-Weinberg equilibrium. In all the 258 parent-proband trios, there were significant transmission disequilibrium in allelic transmission of C, A, T from rs221533, 433E1006, rs3924999 loci respectively (rs221533: chi-square was 27.45, P was 0.000; 433E1006: chi-square was 56.08, P was 0.000; rs3924999: chi-square was 10.53, P was 0.001). Haplotype was analyzed at frequency exceeding 1%. In three-marker-haplotype, C/C/G and C/C/A (marker order: rs221533, rs7820838, 433E1006) transmitted predominantly(C/C/G: chi-square was 5.26, P was 45.08; C/C/A: chi-square was 0.026, P was 0.000). In four-marker-haplotype (marker order: rs221533, rs7820838, 433E1006, rs3924999), C/C/G/T, C/C/A/C and C/C/A/T showed transmission disequilibrium (C/C/G/T: chi-square was 10.71, P was 0.001; C/C/A/C: chi-square was 8.83, P was 0.006, C/C/A/T: chi-square was 27.00, P was 0.000). In the positive subtype of parent-proband trios, C/T/G/C hapoltype transmission was not observed.

CONCLUSIONThe NRG1 gene polymorphism is significantly associated with schizophrenia in Chinese Han, especially in the positive subtype of schizophrenia.