Am J Psychiatry 1996; 153:1530-1533
Copyright © 1996 by American Psychiatric Association
Genetic association of the HLA DRB1 gene locus on chromosome 6p21.3 with schizophrenia
P Wright, PT Donaldson, JA Underhill, K Choudhuri, DG Doherty and RM Murray
Department of Psychological Medicine, Institute of Psychiatry, London, U.K.
OBJECTIVE: The authors investigated the human leukocyte antigen (HLA)
DRB1*04 gene in schizophrenic patients because it is positively associated
with rheumatoid arthritis, an autoimmune disease that exhibits a strong
negative association with schizophrenia. The HLA DQB1*0602 allele was also
studied because of previous reports of genetic association between it and
schizophrenia. Maternal HLA was investigated because of the reported
association between prenatal influenza and schizophrenia and the central
role of HLA molecules in the immune response to viral infections. METHOD:
Polymerase chain reactions and sequence-specific oligonucleotide probes
were used to genotype 94 unrelated patients with DSM-III-R schizophrenia,
92 mothers of schizophrenic offspring who were not related either to each
other or to the 94 patients, and 177 healthy comparison subjects. RESULTS:
The frequency of DRB1*04 alleles was significantly lower in both the
schizophrenic patients and the unrelated mothers of schizophrenic offspring
than in the healthy comparison subjects. No significant differences were
found for DQB1*0602. CONCLUSIONS: DRB1*04 alleles may partially account for
the genetic predisposition to schizophrenia. The association reported here
may be explained by genetic linkage or by an autoimmune pathophysiology for
a proportion of schizophrenia cases. Alternatively, it may be that maternal
B lymphocytes that do not express the DR4 antigen encoded by DRB1*04
respond to influenza virus by producing antibodies that perturb
neurodevelopment, thus underpinning a proportion of schizophrenia cases.
