Transmission disequilibrium analysis of HLA class II DRB1, DQA1, DQB1 and DPB1 polymorphisms in schizophrenia using family trios from a Han Chinese population

Our goal was to evaluate the role of HLA in the risk of developing schizoph renia, in a Han Chinese population. In several Japanese studies, there is e vidence of association with DR1 and schizophrenia. A variety of other assoc iations have been reported in other populations, including negative associa tions with DQ beta *0602 and positive associations with DR1*0101. Using seq uence specific oligonucleotides, we genotyped four HLA markers (DRB1, DQA1, DQB1 and DPB1) in 165 family trios, consisting of Han Chinese schizophreni c subjects and their parents. Individual markers were analysed for transmis sion distortion in the trios using the transmission disequilibrium test. Mu ltiple haplotype transmission was performed using the program TRANSMIT v2.5 . The four markers were in strong linkage disequilibrium with each other(P value from 0.002 to 0). There was no evidence of overall transmission diseq uilibrium for each of the four loci. For DRB1. we did not find transmission distortion for the DRB1*04 and DRB1*08 alleles, as reported previously, bu t the DRB1*03 allele was preferentially not transmitted (P = 0.009). and th e DRB1*13 allele was preferentially transmitted from parents to schizophren ic offspring (P = 0.041). Using haplotypes of pairs of markers. a significa nt global P value of 0.019 was achieved when using DRB1 and DQA1, mainly as a result of the excess transmission of DRB 1*13-DQA1*01 (P = 0.012) and a deficit in transmission of DRB 1*03-DQA1*05 (P = 0.002). In summary, we did not confirm any of the specific HLA allelic associations reported previous ly in Japanese or other populations. However, our results are compatible wi th the view that this region of HLA might contain a susceptibility gene whi ch is in linkage disequilibrium with DRB1 and DQA1 genes. (C) 2001 Elsevier Science B.V. All rights reserved.