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.
BACKGROUND: Both genetics and the environment are implicated as risk factors for prostate cancer (PCa). This populationbased case--control study evaluated four single-nucleotide polymorphisms (SNPs) previously identified by genome-wide association studies to be associated with increased PCa susceptibility. Potential relationships between serum concentrations of phyto-estrogens and SNPs were also investigated. METHODS: Four SNPs (rs10993994, rs2660753, rs1016343 and rs6983267) were genotyped in 247 PCa patients, 125 BPH patients and 274 control men recruited in Scotland. Serum concentrations of the phyto-estrogens enterolactone, equol, genistein and daidzein were measured by isotope dilution gas chromatography--mass spectrometry. RESULTS: Increased PCa risk was associated with TT genotype of rs10993994 compared with CC and CT genotypes combined (odds ratio (OR) ¼ 1.87; 95% confidence interval (CI), 1.26--2.77). TT homozygotes who had low serum enterolactone concentrations (below median) were more likely to have PCa (OR ¼ 2.90; 95% CI, 1.28--6.57) than individuals with CC/CT genotype and high serum enterolactone concentrations (above median). PCa was not associated with the other three SNPs tested. CONCLUSIONS: PCa susceptibility was associated with TT genotype of SNP rs10993994 in this cohort of Scottish men and the increased risk of PCa was modified by serum enterolactone concentrations.
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.
Genome-wide association study (GWAS) suggested that the genes coding for human leukocyte antigens (HLA) were associated with schizophrenia, of which the DRB1*0301, DQA1*0501 and DQB1*0201 variants were strongly associated with a low risk of the illness although the disease-causing variant remains unknown. Haplotype analysis suggested that the haplotypes contraining a HLA-DRB1*13 variant were excessively transmitted by parents to their offspring with schizophrenia in a Chinese population. Accordingly, this study was designed to genotype three HLA-DRB1*13 variants using six HLA-tagging SNPs in a British population to confirm which one of these 3 variants could contribute to the etiology of schizophrenia. Because of the failure of genotyping rs6905141, the DRB1*1302 association was not analysed. While the DRB1*1301 and DRB1*1303 variants were not associated with the disease, the minor allele of rs424232 was used to construct the haplotype tagging to the DRB1*1303 variant showed a strong association with a low risk of schizophrenia (p = 0.002), suggesting that the major allele of rs424232 may be in linkage disequilibrium with a disease-underlying vatriant. In conclusion, the HLA-DRB1*13 variants are unlikely to be involved in the development of schizophrenia but there may be a variant nearby which is involved.
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