Association study between the MDR1 gene and clinical characteristics in schizophrenia

Abstract

Objective: Schizophrenia is a complex psychiatric disorder, characterized by disturbed patterns of thought and affecting 0.3-2.0% of the world population. Previously, the multidrug resistance 1 (MDR1) gene has been associated with schizophrenia in treatment response studies in psychotic patients. The aim of this study was to determine the association between MDR1 gene polymorphisms and clinical characteristics in patients with schizophrenia. Methods: Positive and negative symptoms of schizophrenia were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) in 158 Mexican patients with schizophrenia. Analyses of MDR1 gene polymorphisms were performed using TaqMan technology. A multivariate ANOVA was performed with MDR1 polymorphisms and gender as independent variables. Results: Males with the G/G genotype of MDR1 rs2032582 presented significantly higher levels of delusions (p = 0.02). When comparing female vs. male groups, the difference was statistically significant (p = 0.0003). Analyses of the MDR1 gene rs1045642 variant showed no significant differences. Conclusion: Our findings suggest that male carriers of the G allele of variant rs2032582 exhibit greater severity of delusions; however, these results should be taken as preliminary, and replication studies in other populations of different ethnic origins are required to confirm these findings.

Evaluation of the Role of ABCB1gene Polymorphic Variants on Psychiatric Disorders Predisposition in Macedonian Population

“…The results from our study have confirmed fourfold increased risk for psychiatric disorder in women that are heterozygous for 1236 and 2677 polymorphisms in comparison with the whole control group (men and women), and three-fold higher risk in comparison to control group only with women and such difference wasn't seen in male population. Tovilla-Zárate et al, 2014 confirmed significant association of 2677GG polymorphic variant with severity of particular symptoms in hallucinations and delusions in male patients with schizophrenia [42] .Although, the mechanism by which this non-synonymous polymorphism influence the predisposition for psychiatric illnesses or the severity of the symptoms is still not determined, it could be assumed that mutant P-glycoprotein with replaced hydro-philic Ser with more lipophilic Thr/Ala is less substrate-specific [43].…”

Genetic Basis of Positive and Negative Symptom Domains in Schizophrenia

“…Genes associated with positive, but not negative, symptoms of schizophrenia include multidrug resistance 1 (MDR1), which encodes for P-gp, a transmembrane drug transporter in the blood-brain barrier. Polymorphisms of this gene were associated with hallucinations and bizarre behavior in a Mexican sample, although the functional mechanisms of this association are unknown (Tovilla-Zárate et al, 2014). Rare duplication burden has been negatively correlated with positive symptoms (Martin, Robinson, Reutens, & Mowry, 2015a), whereas common genetic variant burden calculated as a polygenic risk profile score was positively associated with positive symptoms (Martin, Robinson, Reutens, & Mowry, 2015b).…”

The influence of genetic and epigenetic factors as covariates of the tolerability and therapeutic response to olanzapine in the treatment of psychotic diseases

“…Alela T byla v menší studii asociována s lepší odpovědí na léčbu v pozitivní škále PANSS (24). Na druhou stranu byla alela G asociována s těžšími bludy (37).…”