Povezanost terapijske rezistencije u oboljelih od shizofrenije i varijabilnosti gena DAT, SERT i MDR1/ABCB1

Bilić, Petar (2014) Povezanost terapijske rezistencije u oboljelih od shizofrenije i varijabilnosti gena DAT, SERT i MDR1/ABCB1. PhD thesis, Sveučilište u Zagrebu.

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Abstract

One fifth to one third of all patients diagnosed with schizophrenia are resistant to drug treatment. We explored associations between carefully characterized TRS and DAT-VNTR, SERTPR, SERT-in2 and MDR1/ABCB1 polymorphisms. There were 173 patients enrolled in the study that were clinically evaluated using Positive and Negative Syndrome Scale and Clinical Global Impressions Scales and divided into two groups based on treatment resistance (92 patients in TRS group). Carriers of SERT-PR 'SS' genotype were more less likely to have TRS (OR = 0.4; 95% CI = 0.20 - 0.94). Patients with a combination of SERT-in2 ll and DAT 9/10, 9/11, 9/9 and 6/6 genotype were more likely to have TRS, compared to those with 10/10 or 10/12 genotype (OR = 5.1; 95% CI = 1.6-16.8). In the group of patients with DAT 10/10 or 10/12 genotype, those who also shared SERT-in2 ls or ss genotype were more likely to have TRS, compared to ll genotype carriers (OR = 2.7; 95% CI = 1.0-7.0). The model in which interaction between SERT-in2 and DAT polymorphisms is linked to TRS can possibly explain contradictory previous results regarding role of DAT and SERT in TRS. There were no statistical significant associations between TRS and MDR1/ABCB1 polymorphisms. Further researches are needed.

Abstract in Croatian

Petina do trećina oboljelih od shizofrenije pripada terapijski rezistentnim bolesnicima (TRS). Istraživali smo povezanost oboljelih od shizofrenije koji jasno ispunjavaju kriterije terapijske rezistencije s polimorfizmima DAT-VNTR, SERTPR, SERT-in2 i MDR1/ABCB1 gena. U istraživanje je uključeno 173 bolesnika, od kojih je 92 bolesnika bilo TRS. Bolesnici su klinički procijenjeni 'pozitivnom i negativnom sindromskom ljestvicom' (PANSS) i 'kliničkom ljestvicom općeg dojma' (CGI-S i CGI-I), te ljestvicom 'opće razine funkcioniranja' (GAF). Nosioci SERTPR 'SS' genotipa su imali manju šansu razvijanja TRS (OR = 0.4; 95% CI = 0.20 - 0.94). Bolesnici sa kombinacijom SERT-in2 'll' i DAT '9/10', '9/11', '9/9' i '6/6' genotipa su imali veću šansu postati TRS u usporedbi s nosiocima '10/10' ili '10/12' genotipe (OR = 5.1; 95% CI = 1.6-16.8). U skupini bolesnika s DAT 10/10 ili 10/12 genotipom oni koji su nosioci SERT-in2 'ls' ili 'ss' genotipa su imali veću šansu postati TRS u usporedbi s 'll' genotipom (OR = 2.7; 95% CI = 1.0-7.0). Model u kojemu je interakcija između SERT-in2 i DAT polimorfizama povezana s TRS možda može objasniti prethodne oprečne rezultate koji se odnose na DAT i SERT polimorfizam TRS. Nije bilo statistički znaĉajne povezanosti između TRS i MDR1/ABCB1 polimorfizama. Potrebna su daljnja istraživanja.

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