β2 microglobulin, HLA-A and Notch4 were all expressed in a pattern where inflammatory illness was associated with increased expression in controls but not in subjects with schizophrenia.
The present study investigated frequencies of HLA-A specificities in schizophrenia patients (ICD-10 and DSM-III-R, n=98) and sex-matched healthy controls (n=392) from population in the southwestern part of Japan.
Here, we report the results of a family-based candidate-gene study that brings together these two disparate lines of research by assessing maternal-fetal genotype matching at HLA-A, -B, and -DRB1 as a risk factor of schizophrenia.
β2 microglobulin, HLA-A and Notch4 were all expressed in a pattern where inflammatory illness was associated with increased expression in controls but not in subjects with schizophrenia.
However, no significant differences of these allelic frequencies were found between the patients and the control subjects, suggesting that the HLA-A gene was unlikely a major risk factor of schizophrenia in this sample.
However, no significant differences of these allelic frequencies were found between the patients and the control subjects, suggesting that the HLA-A gene was unlikely a major risk factor of schizophrenia in this sample.
While searching for the "true" disease gene near the HLA-A gene, we discovered that homozygosity of the HLA-J M80469 pseudogene allele, in combination with HLA-A10 or HLA-A9, was associated with a high risk of schizophrenia (HLA-A10 relative risk = 29.33, p = 0.00019, patients N = 77, controls N = 214).
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.
While searching for the "true" disease gene near the HLA-A gene, we discovered that homozygosity of the HLA-J M80469 pseudogene allele, in combination with HLA-A10 or HLA-A9, was associated with a high risk of schizophrenia (HLA-A10 relative risk = 29.33, p = 0.00019, patients N = 77, controls N = 214).
Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.
Carrier frequencies of HLA-A*02:07 in patients with zonisamide-induced SJS/TEN and in the general Japanese population were 41.7 and 6.81%, respectively.
Associations between HLA and carbamazepine hypersensitivity reactions demonstrate both ethnicity and phenotype specificity; with HLA-B*15:02 associated with Stevens-Johnson syndrome and toxic epidermal necrolysis in South East Asian patients only whilst HLA-A*31:01 is associated with all phenotypes of hypersensitivity in multiple ethnicities.
The variant allele HLA-A*31:01 is associated with greater risk of maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms, and SJS/TEN in patients treated with carbamazepine.
We focused on 80 Indian patients with SJS/TEN with severe ocular complications (SOC) and investigated the association of alleles at HLA -A, HLA-B and HLA-C loci; the controls were 50 healthy Indian volunteers.
SJS and TEN were found to be significantly associated with HLA-A*33:03 and HLA-C*03:02 alleles in both groups of studies with matched controls and population controls.
Allergic drug reactions are unpredictable; nevertheless, there is increased risk of drug hypersensitivity in (1) patients with cystic fibrosis who receive antibiotics; (2) patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) who receive trimethoprim-sulfamethoxazole or if human leukocyte antigen (HLA)-B*5701+ and receive the antiretroviral agent abacavir; (3) other genetically susceptible populations, e.g., Han-Chinese with HLA-B*1502+ who develop Stevens-Johnson syndrome and toxic epidermal necrolysis from carbamazepine, with HLA-B*5801+ who are at increased risk for such reactions from allopurinol, those with HLA-A*32:01 and receive vancomycin and develop drug reaction with eosinophilia and systemic symptoms syndrome; and (4) patients with a history of compatible allergic reactions to the same medication, similar class, or potentially unrelated medication.
The frequencies of HLA-A*33:03 as well as C*03:02 and C*08:01 were significantly higher in SJS/TEN patient subgroup showing allopurinol drug-induced severe cutaneous adverse reactions (SCAR) as compared to controls (28.6% vs 0%, P=0.00002, Pc=0.0011; 28.6% vs 0%, P=0.00002, Pc=0.001; 28.6% vs 0%, P=0.00002, Pc=0.001, respectively).
Increasing studies reported genetic susceptibility to drug hypersensitivity reactions, as exemplified by the HLA-A*31:01 and HLA-B*15:02 association with carbamazepine (CBZ)-induced hypersensitivity reactions, such as maculopapular exanthema (MPE), drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).