Dataset Information

The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report.

ABSTRACT: Despite the high prevalence of depression, the mechanism of the origin of this disease as well as the causes of resistance to therapy in some patients are still not fully understood. Increasingly, the possible role of genetic factors is considered. One of them is polymorphisms in the ABCB1 (MDR1) gene which encodes P-glycoprotein, responsible for the transport of xenobiotics, including antidepressant drugs, through the blood-brain barrier.C3435T was evaluated in 90 patients with recurrent depressive disorders (rDD). Genotyping was performed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).The obtained results indicate that the TT genotype occurred more frequently among patients with rDD than in healthy volunteers (p=0.0441). Also, at least one C allele was present significantly less frequent in the study group than in healthy individuals (p=0.0300). The severity of depressive symptoms was higher among patient with the CC genotype in comparison with the other genotypes (p=0.0106) but treatment response to antidepressants was better in this group than among patients with CT or TT genotypes (p=0.0301). Likewise, patients with the T allele have a significantly lower severity of symptoms (p=0.0026) and decreased therapy effectiveness (p=0.0142) than C allele carriers.This study suggests that C3435T polymorphisms in the ABCB1 gene are strongly associated with a predisposition to depression development, the severity of depressive symptoms and the effectiveness of therapy with using different groups of antidepressant agents.

SUBMITTER: Jelen AM

PROVIDER: S-EPMC4661296 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report.

Jeleń Agnieszka Maria AM Sałagacka Aleksandra A Żebrowska Marta Karolina MK Mirowski Marek M Talarowska Monika M Gałecki Piotr P Balcerczak Ewa Izabela EI

International journal of medical sciences 20151120 12

<h4>Background</h4>Despite the high prevalence of depression, the mechanism of the origin of this disease as well as the causes of resistance to therapy in some patients are still not fully understood. Increasingly, the possible role of genetic factors is considered. One of them is polymorphisms in the ABCB1 (MDR1) gene which encodes P-glycoprotein, responsible for the transport of xenobiotics, including antidepressant drugs, through the blood-brain barrier.<h4>Methods</h4>C3435T was evaluated i ...[more]

PMID: 26664259

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Project description:PurposeEpilepsy is a disease of neurological character. Approximately one third of epileptic patients demonstrate a drug-resistant phenotype, which is associated with the development of drug-resistant epilepsy. The multidrug resistance protein 1 and glycoprotein P, encoded by MDR1, play a significant role in the transmembrane transport of anti-epileptic agents. Single nucleotide polymorphism C3435T (rs1045642) within MDR1 gene may be associated with an increased expression of P-gp which affects the levels of antiepileptic drugs in plasma. The presented studies analysed the association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children.MethodsC3435T polymorphism of MDR1 gene was analysed by the high resolution melting technique in a group of patients with drug-resistant (n = 106) and drug-responsive epilepsy (n = 67), as well as in non-epileptic children (n = 98) hospitalised at the Department of Neurology, Polish Mother's Memorial Hospital in Lodz. Genotype and allele distributions were evaluated and their compatibility with the Hardy-Weinberg distribution was assessed by means of the χ(2) test. Genotype and allele evaluation, regarding their relationship with a given feature, was supported by an analysis of odds ratio and 95 % confidence interval, calculated according to the logistic regression model.ResultsAn association was observed between the incidence rate of DRE and the presence of C allele in C3435T polymorphism of MDR1 gene, which may enhance the risk of the disease. The T allele may then play a protective role. No differences were found in the studied groups, regarding either genotype or allele distribution in reference to patient's gender or concomitant diseases.ConclusionFollowing the obtained results, C3435T polymorphism of MDR1 gene may be connected with the incidence of drug-resistant epilepsy in the population of Polish children. ISRCTN ISRCTN73824458. Registered 28th September 2014.

Project description:BackgroundBreast cancer is the most common cause of cancer death among women. Several studies have investigated the relationship between the C3435T polymorphism of ABCB1 gene and risk of breast cancer; but the results are conflicting. In the present study, we sought to assess the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in a sample of the Moroccan population.MethodsA case control study was performed on 60 breast cancer patients and 68 healthy women. The ABCB1 C3435T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Furthermore, a meta-analysis including 16 studies with 6094 cases of breast cancer and 8646 controls was performed.ResultsGenotype frequencies were 50 % for CC, 33.3 % for CT and 16.7 % for TT in patients and 41.2 % for CC, 48.5 % for CT and 10.3 % for TT respectively in the control group. This difference was not statistically significant. The same trend as observed in the allele distribution between patients and controls (P = 0.84). Findings from the meta-analysis showed that the ABCB1 C3435T polymorphism was not associated with an increased risk of breast cancer in the dominant model (OR = 0.907; 95 % CI = 0.767-1.073; P = 0.25) as well as in the recessive model (OR = 1.181; 95 % CI = 0.973-1.434; P = 0.093) and in the allele contrast model (OR = 1.098; 95 % CI = 0.972-1.240; P = 0.133). However, the stratification of studies on ethnic basis showed that the TT genotype was associated with the risk of breast cancer in Asians (OR = 1.405; 95 % CI = 1.145-1.725; P = 0.001), Caucasians (OR = 1.093; 95 % CI = 1.001-1.194; P = 0.048) and North African (OR = 2.028; 95 % CI = 1.220-3.371; P = 0.006).ConclusionsWe have noted that the implication of C3435T variant on the risk of breast cancer was ethnicity-dependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.

Dataset Information

The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report.

Publications

The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report.

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