Search for schizophrenia susceptibility variants at the HLA-DRB1 locus among a British population.

Schizophrenia is a complex mental disorder with unknown aetiology. Both candidate gene and genome-wide association (GWA) studies suggest that the human leukocyte antigen (HLA) system may play a part in development of the illness, but the causal HLA variant(s) remain(s) unclear. Previous studies showed that the DRB1*0101 and DRB1*13 alleles might be associated with a high risk of schizophrenia. Therefore, the present study was undertaken to test their association with the disease by genotyping seven DRB1-tagging single nucleotide polymorphisms (SNPs) in a British population. The results showed that, of the previously reported variants that were associated with schizophrenia, the DRB1*1303 allele was the only one marginally associated with a protective effect on the illness in our sample set (χ² = 4.138, P = 0.042, odds ratio (OR) = 0.42, 95 % confidence interval (CI) 0.27-0.66). Interestingly, a significant association was found for rs424232 (χ² = 9.404, P = 0.002, OR = 0.69, 95 % CI 0.54-0.88), which is a tag SNP for the DRB1*1303 allele and located near to the NOTCH4 gene that is a schizophrenia susceptibility locus confirmed by GWA studies. Analysis with the Haploview program demonstrated that rs424232 was in complete linkage disequilibrium with rs3130297 and rs3131296 present in the NOTCH4 locus. While we have failed to confirm association of the candidate alleles in the DRB1 gene with a high risk of schizophrenia, the present work suggests that the association signal detected in the HLA class II locus may extend a relatively long distance, and more work is needed in order to identify the true causal variants within this region or nearby.

No correlation between HLA-DQ 2.5, DQ 8.1 and DQ 6.2 and circulating levels of antibodies against gliadins in schizophrenia.

It has been suggested that gluten consumption is linked to schizophrenia, with this link strengthened through the presence of circulating anti-native gliadin antibodies (AGAs). The human leukocyte antigen (HLA) system is crucial for antigen presentation and antibody secretion but no study has examined the relationship between HLA-II variants and circulating antibodies against gliadin peptides. In this study, HLA-II variants were genotyped in patients with schizophrenia and the relationship between these variants and plasma AGA levels was examined. Although there was no association found, HLA-AGA associations could potentially serve as a marker of gluten sensitivity in patients with schizophrenia.

A study of type-1 diabetes associated autoantibodies in schizophrenia.

Epidemiological studies revealed an association between type-1 diabetes (T1D) and schizophrenia but the findings reported to date have been controversial. To clarify the inconsistency across studies, T1D-associated autoantibodies were examined in plasma samples collected from 272 patients with schizophrenia and 276 control subjects. An in-house enzyme-linked immunosorbent assay (ELISA) was developed using three linear peptide antigens, one of which was derived from glutamic acid decarboxylase (GAD) and two were derived from insulinoma-associated antigen 2 (IA2). Mann-Whitney U test showed a significant decrease in the levels of plasma IgG against the IA2b antigen in schizophrenia patients as compared to control subjects (Z=-3.54, p=0.0007), while no significant difference was found between these two groups either in anti-IA2a IgG levels (Z=-1.62, p=0.105) or in anti-GAD IgG levels (Z=-1.63, p=0.104). Linear regression analysis indicated no association of antipsychotic medication with the levels of plasma IgG against IA2a, IA2b or GAD, while the levels of plasma IgG for these 3 peptide antigens were significantly correlated with each other. Binary logistic regression showed that neither the DQ2.5 variant nor the DQ8 variant was associated with circulating levels of 3 T1D-associated autoantibodies in both the patient group and the control group. The coefficient of variation was 10.7% for anti-IA2a IgG assay, 10.1% for anti-IA2b IgG assay and 10.7% for anti-GAD IgG assay. The present work suggests that T1D-associated antibodies are unlikely to confer risk of schizophrenia and that the in-house ELISA developed with linear peptide antigens is highly reproducible.