Role of the enzymes of dopamine biodegradation in the pathogenesis of panic disorder and psoriasis

Klimov, E.A.; Gapanovich, E.S.; Azimova, J.E.; Rudko, O.I.; Kokaeva, Z.G.; Sakaniya, L.R.; Korsunskaya, I.M.; Danilin, I.E.; Sobolev, V.V.

Авторы: Klimov E.A., Gapanovich E.S., Azimova J.E., Rudko O.I., Kokaeva Z.G., Sakaniya L.R., Korsunskaya I.M., Danilin I.E., Sobolev V.V.
Сборник: Abstracts from the 16th Congress of the European Society for Dermatology and Psychiatry
Серия: Acta dermato-venereologica. Vol 96, Suppl 217: 113–152
Том: 96
Год издания: 2016
Место издания: Uppsala: Society for the Publication of Acta Dermato-Venereologica Uppsala, Sweden
Первая страница: 133
Последняя страница: 133
DOI: 10.2340/00015555-2158
Аннотация: Introduction. The comorbidity of psoriasis and depression, anxiety and other psychosocial disorders was shown (Rieder, Tausk, 2012; Zeljko-Penavic et al., 2013). Previously, we have shown the effect of polymorphisms of genes encoding catechol-O-methyltransferase (COMT) and dopamine beta-hydroxylase (DBH) on the pathogenesis of panic disorder. The aim of this work - to reveal the association of polymorphic variants of COMT gene (c.472G>A) and DBH gene (Ins/Del) with psoriasis. Materials and methods. We used DNA samples of patients diagnosed with psoriasis (n = 88) and unscreened residents of Moscow as a control (n = 363). Molecular genetic analysis conducted by allele-specific PCR (DBH) and real-time PCR (COMT). Statistical processing was performed using chi-square test. The search for associated complex haplotypes was performed using APSampler 3.6.1 software. Results and discussion. Association with the disease detected only for COMT gene: genotype AG (chi-square=10.57, p=0, OR=3.54, CI (95%)=2.00-6.29). During the analysis of complex haplotypes was revealed a combination of alleles of studied genes that contribute to the pathogenesis of the disease: COMT:G,A + DBH:Del (Fisher p=2.13e-06, OR=3.85, CI (95%)=[2.18-6.80], Correction Bonferroni p=0.00012) and COMT:A + DBH:Del (Fisher p=0.00036, OR=2.71, CI (95%)=[1.54-4.79], Correction Bonferroni p=0.02). Both enzymes involved in biosynthesis of dopamine, using it as a substrate. DBH is synthesized norepinephrine from dopamine. A deletion in the 5'-region of the DBH gene linked to low level of its plasma activity. This leads to the accumulation of dopamine. Substitution in COMT gene (c.472G>A) causes an amino acid substitution p.Val158Met. The enzyme containing Met at position 158, shown 3-4 fold lower activity than wild-type Val. COMT methylates dopamine to form 3'-methoxytyramine. The decrease COMT activity also leads to the accumulation of dopamine. The second complex haplotype COMT:A + DBH:Del, although has less power, but indicates a role of decrease in enzymes activity in the pathogenesis of psoriasis. This suggests a role for dopamine excess in the pathogenesis of psoriasis. Conclusion. Thus, we show the effect on the pathogenesis of psoriasis polymorphisms of genes involved in the metabolism of dopamine and previously associated with panic disorder. This suggests the role of abnormalities in the functioning of neurotransmitter systems in the pathogenesis of psoriasis.
Добавил в систему: Климов Евгений Александрович

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Role of the enzymes of dopamine biodegradation in the pathogenesis of panic disorder and psoriasisстатья

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