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

Abstract

Our goal was to evaluate the role of HLA in the risk of developing schizophrenia, in a Han Chinese population. In several Japanese studies, there is evidence of association with DR1 and schizophrenia. A variety of other associations have been reported in other populations, including negative associations with DQβ ∗0602 and positive associations with DR1 ∗0101. Using sequence specific oligonucleotides, we genotyped four HLA markers (DRB1, DQA1, DQB1 and DPB1) in 165 family trios, consisting of Han Chinese schizophrenic subjects and their parents. Individual markers were analysed for transmission distortion in the trios using the transmission disequilibrium test. Multiple 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 disequilibrium 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, but the DRB1 ∗03 allele was preferentially not transmitted ( P=0.009), and the DRB1 ∗13 allele was preferentially transmitted from parents to schizophrenic offspring ( P=0.041). Using haplotypes of pairs of markers, a significant global P value of 0.019 was achieved when using DRB1 and DQA1, mainly as a result of the excess transmission of DRB1 ∗13–DQA1 ∗01 ( P=0.012) and a deficit in transmission of DRB1 ∗03–DQA1 ∗05 ( P=0.002). In summary, we did not confirm any of the specific HLA allelic associations reported previously in Japanese or other populations. However, our results are compatible with the view that this region of HLA might contain a susceptibility gene which is in linkage disequilibrium with DRB1 and DQA1 genes.