Association of TLR3 gene polymorphism with IgG subclass deficiency and the severity in patients with aspirin-intolerant asthma

PURPOSE: Toll-like receptor 3 (TLR3) recognizes to viral double-stranded RNA and is involved in antiviral defenses. A probable role of TLR3 gene variants in the pathogenesis of aspirin-intolerant asthma (AIA) has been suggested. AIA patients present more frequent asthma exacerbations in which respiratory viral infections could be an exacerbating factor. IgG subclass deficiency was commonly present with bronchial asthma. Based on previous findings, we investigated whether TLR3 variants could affect IgG3 subclass deficiency in AIA. METHODS: We enrolled 279 AIA patients, 403 aspirin-tolerant asthma (ATA) patients, and 315 normal healthy controls (NC) in this study. TLR3 polymorphism at the promoter region -299698G>T was genotyped. The serum levels of IgG subclasses were determined by the single radial immunodiffusion method. Expressions of IgG3 and TLR3 on Epstein-Barr virus transformed-B cells isolated from asthmatic patients were evaluated by flow cytometry to investigate B-cell functions. RESULTS: The TLR3 -299698 T allele was significantly associated with severity and IgG3 deficiency in the AIA group (P=0.044 and P=0.010, respectively), but not in the ATA group. IgG3 expression on B cells from asthmatics with IgG3 deficiency was significantly lower compared to those without (P=0.025). There was a positive correlation between IgG3 expression levels on B cells and serum IgG3 levels (r 2=0.434, P=0.002). CONCLUSION: These results suggest that the TLR3 -299698G>T polymorphism may be associated with IgG3 subclass deficiency and severity in AIA.

Sex-Related Differences of EEG Coherences between Patients with Schizophrenia and Healthy Controls

OBJECTIVES: Alteration of epigenetic effects of testosterone during early development was suggested as an ancillary mechanism for the genesis of schizophrenia. EEG coherence was thought to be a marker for cerebral laterality of which important determinant was testosterone during early development. We studied sex-related differences of EEG coherences between patients with schizophrenia and controls to examine the sex effects in the genesis of schizophrenia. METHODS: EEG was recorded in 35 patients with schizophrenia and 46 healthy controls in the eyes closed resting state. Pair-wise EEG coherences were calculated over delta, theta, alpha, beta and gamma frequency bands. To examine the differences of EEG coherence according to sex in each group, ANCOVA was performed using Statistical Analysis system (SAS, Ver 9.3) and R (Ver 2.15.2). RESULTS: Healthy control males showed more increased right intrahemispheric coherences than healthy control females in delta, theta, alpha and beta frequency bands. In patients with schizophrenia, this male dominant pattern in right intrahemispheric coherences was attenuated especially in alpha and beta bands. Healthy control females showed more increased interhemispheric coherences than healthy control males in delta, theta, beta and gamma frequency bands. In patients with schizophrenia, these female dominant patterns in interhemispheric coherences were attenuated especially in delta, theta, and beta bands, which were commonly observed in frontal to central areas. CONCLUSION: Sex differences in resting EEG coherences were attenuated in schizophrenia patients. These results imply that sex-related aberrant cerebral lateralization might exist in patients with schizophrenia, which are partly due to sex hormones via epigenetic mechanisms.