hrvatski

Učinak polimorfizama u genima za cPLA2 i COX-2 na oslabljenu niacinsku reakciju kože u bolesnika sa shizofrenijom

Objective: Attenuated niacin skin-flush response potentially marks the cytosolic phospholipase A2/cyclooxygenase-2 (cPLA2/COX-2) cascade abnormalities. Genetic polymorphisms of genes involved in cPLA2/COX-2 pathway, and their impact on the niacin skin-flush response were investigated in patients with schizophrenia. Methods: Allelic/genotypic frequencies of BanI polymorphism of the cPLA2 gene and A/G variant (rs689466) of the COX-2 gene were determined in 204 Croatian patients and 191 controls by PCR-RFLP analysis. Patches containing 0.1M, 0.01M, 0.001M and 0.0001M solutions of aqueous methyl nicotinate (AMN) were kept for 5 minutes on the forearm skin in 80 patients and 80 controls and visual evaluation of flushing rated from 0 to 3 was done in 5 minute intervals up to 15 minutes by two independent raters. Results: Allelic/genotypic frequencies between patients and controls were not significantly different. Controls showed significantly higher flushing at all concentrations and minute intervals (P<0.001). Multiple regression analysis revealed that AMN concentration (β=0.65), minute interval (β=0.26), GG genotype of cPLA2 (β=0.16), and COX-2 polymorphism (β=0.14) were significant predictors of the flush response. The presence of cPLA2-GG genotype correlated significantly with flushing at higher AMN concentrations (0.1M and 0.01M) and at all time points. Weaker, but statistically significant correlation between flushing and COX-2 genotype was determined at 0.001M concentrations. Regarding flush response, there was no synergy between two polymorphisms. We revealed significant interaction between cPLA2-GG genotype and AMN concentration on niacin response at 10-minute interval.Conclusions: Niacin response was significantly attenuated in patients compared to controls. Both polymorphisms impacted niacin sensitivity in the patient group.

shizofrenija ; polimorfizmi jednog nukleotida u genima PLA2G4A i PTGS2 ; reakcija kože na niacin

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