GENETIC ASSOCIATION OF THE HLA DRB1 GENE LOCUS ON CHROMOSOME 6P21.3 WITH SCHIZOPHRENIA

Objective: The authors investigated the human leukocyte antigen (HLA) DRB104 gene in schizophrenic patients because it is positively associ ated with rheumatoid arthritis, an autoimmune disease that exhibits a strong negative association with schizophrenia. The HLA DQB10602 alle le was also studied because of previous reports of genetic association between it and schizophrenia. Maternal HLA was investigated because o f the reported association between prenatal influenza and schizophreni a and the central role of HLA molecules in the immune response to vira l infections. Method: Polymerase chain reactions and sequence-specific oligonucleotide probes were used to genotype 94 unrelated patients wi th DSM-III-R schizophrenia, 92 mothers of schizophrenic offspring who were not related either to each other or to the 94 patients, and 177 h ealthy comparison subjects. Results: The Frequency of DRB104 alleles was significantly lower in both the schizophrenic patients and the unr elated mothers of schizophrenic offspring than in the healthy comparis on subjects. No significant differences were found for DQB10602. Conc lusions: DRB104 alleles may partially account fbr the genetic predisp osition to schizophrenia. The association reported here may be explain ed by genetic linkage or by an autoimmune pathophysiology for a propor tion of schizophrenia cases. Alternatively, it may be that maternal B lymphocytes that do not express the DR4 antigen encoded by DRB104 res pond to influenza virus by producing antibodies that perturb neurodeve lopment, thus underpinning a proportion of schizophrenia cases.