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The association between COMT Val158Met and BDNF Val66Met genotypes and antipsychotic induced side effects (CROSBI ID 592659)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Pivac, Nela ; Nikolac, Matea ; Uzun, Suzana ; Nedić, Gordana ; Kozumplik, Oliver ; Muck-Šeler, Dorotea The association between COMT Val158Met and BDNF Val66Met genotypes and antipsychotic induced side effects // Proceedings of the British Pharmacological Society a. 2012. str. 1-1

Podaci o odgovornosti

Pivac, Nela ; Nikolac, Matea ; Uzun, Suzana ; Nedić, Gordana ; Kozumplik, Oliver ; Muck-Šeler, Dorotea

engleski

The association between COMT Val158Met and BDNF Val66Met genotypes and antipsychotic induced side effects

Patients with psychotic disorders frequently develop side effects after antipsychotic treatment. Pharmacogenetic studies reported significant associations, but also the lack of associations, between the genetic variants of catechol-o-methyltransferase (COMT Val158Met)and brain-derived neurotraphic factor (BDNF Val66Met) and particular antipsychotic-induced side effects. Since atypical antipsychotics frequently induce metabolic side effects, the aim of the study was to evaluate the association between antipsychotic-induced side effects and genetic variants of COMT Val158Met and BDNF Val66Met. The study included 128 male and female patients with schizophrenia (diagnosed using Structured clinical interview based on DSM-IV criteria) who were treated for 6 months with atypical antipsychotics (clozapine 25-500 mg/d, risperidone 1-10 mg/d, olanzapine 5-20 mg/d, quetiapine 50-800 mg/d). Patients were subdivided into non-risk and risk groups based on: body mass index (BMI) (higher than 25), glucose (higher than 6.1 mmol/L), high density lipoprotein (HDL) cholesterol (for women lower than 1.3mmol/L ; for men lower than 1.0 mmol/L), waist circumference (for women higher than 88 cm ; for men higher than 102 cm), blood pressure (higher than 130/85 mm Hg), triglycerides (higher than 1.7 mmol/L), and presence/absence of the metabolic syndrome. COMT Val158Met (rs4680) and BDNF Val66Met (rs6265) genotypes were determined using the TaqMan SNP Genotyping Assay. Results were evaluated using χ2 test and one-way ANOVA. In all patients waist circumference (F=3.447 ; P=0.035) and triglyceride concentrations (F=4.289 ; P=0.021) were significantly lower in carriers of COMT Met/Met genotype than in other COMT genotypes. When patients were subdivided according to gender, the frequency of BDNF Val66Met genotypes differed significantly (χ2=9.740 ; P=0.0076) between male risk and non-risk groups according to glucose concentration. Male carriers of BDNF Met/Met genotype had significantly (F=5.211 ; P=0.010) lower plasma glucose concentration than carriers of BDNF Met/Val or Val/Val genotypes. In female patients, the distribution of COMT Val158Met genotypes was significantly different between risk and non-risk groups according to triglyceride concentration (χ2=7.413 ; P=0.0246). ANOVA revealed that female carriers of COMT Met/Met genotype had significantly lower waist circumference (F=5.077 ; P=0.008) and BMI (F=3.163 ; P=0.047) than female carriers of COMT Met/Val or Val/Val genotypes. Other side effects were not significantly (P > 0.05) associated with COMT Val158Met or BDNF Val66Met genotypes. In conclusion, BDNF Val66Met was significantly associated with the risk of higher glucose concentration in male patients, while COMT Val158Met was significantly associated with the risk of increased triglyceride concentration, waist circumference and BMI in female patients. Both BDNF and COMT Met/Met genotype carriers had significantly lower values than carriers of other genotypes. This preliminary pharmacogenetic study revealed sex-related differences and significant association between atypical antipsychotic-induced side effects and COMT Val158Met or BDNF Val66Met. Therefore, further studies should enlarge the groups to elucidate whether COMT Val158Met or BDNF Val66Met might be used as markers of metabolic side effects, with aim to improve treatment response and compliance and to reduce health risk.

catechol-O-methyltransferase (COMT) ; brain-derived neurotrophic factor (BDNF) ; antipsychotics ; side effects

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Podaci o prilogu

1-1.

2012.

nije evidentirano

objavljeno

Podaci o matičnoj publikaciji

Proceedings of the British Pharmacological Society a

Podaci o skupu

6th European Congress on Pharmacology EPHAR 2012

poster

17.07.2012-20.07.2012

Granada, Španjolska

Povezanost rada

Temeljne medicinske znanosti

Poveznice