Dataset Information

Genetic Polymorphisms of Multidrug Resistance Gene-1 (MDR1/ABCB1) and Glutathione S-Transferase Gene and the Risk of Inflammatory Bowel Disease among Moroccan Patients.

ABSTRACT: Inflammatory bowel diseases (IBD) are multifactorial disorders resulting from environmental and genetic factors. Polymorphisms in MDR1 and GSTs genes might explain individual differences in susceptibility to IBD. We carried out a case-control study to examine the association of MDR1 (C1236T and C3435T), GSTT1, and GSTM1 polymorphisms with the risk of IBD. Subjects were genotyped using PCR-RFLP for MDR1 gene and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was performed to test the association of variant allele carriage with IBD risk. We report that GSTT1 null genotype is significantly associated with the risk of CD (OR: 2.5, CI: 1.2-5, P = 0.013) and UC (OR: 3.5, CI: 1.5-8.5, P = 0.004) and can influence Crohn's disease behavior. The interaction between GSTT1 and GSTM1 genes showed that the combined null genotypes were associated with the risk of UC (OR: 3.1, CI: 1.1-9, P = 0.049). Furthermore, when compared to combined 1236CC/CT genotypes, the 1236TT genotype of MDR1 gene was associated with the risk of UC (OR: 3.7, CI: 1.3-10.7, P = 0.03). Meta-analysis demonstrated significantly higher frequencies of 3435T carriage in IBD patients. Our results show that GSTT1 null and MDR1 polymorphisms could play a role in susceptibility to IBD.

SUBMITTER: Senhaji N

PROVIDER: S-EPMC4641206 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genetic Polymorphisms of Multidrug Resistance Gene-1 (MDR1/ABCB1) and Glutathione S-Transferase Gene and the Risk of Inflammatory Bowel Disease among Moroccan Patients.

Senhaji Nezha N Kassogue Yaya Y Fahimi Mina M Serbati Nadia N Badre Wafaa W Nadifi Sellama S

Mediators of inflammation 20151028

Inflammatory bowel diseases (IBD) are multifactorial disorders resulting from environmental and genetic factors. Polymorphisms in MDR1 and GSTs genes might explain individual differences in susceptibility to IBD. We carried out a case-control study to examine the association of MDR1 (C1236T and C3435T), GSTT1, and GSTM1 polymorphisms with the risk of IBD. Subjects were genotyped using PCR-RFLP for MDR1 gene and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was performed to test the associatio ...[more]

PMID: 26604430

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Project description:ObjectiveTo analyse the single-nucleotide polymorphisms (SNPs): ABCB1(1236C>T), ABCB1(2677G>T/A), ABCB1(3435C>T) and haplotypes in the ABCB1/MDR1 gene, which could contribute to genetic risk of colorectal cancer (CRC). Disease association between the ABCB1/MDR1 genotype, allele, haplotype frequencies and histological features, such as TNM classification, localization of primary carcinoma, grade of malignancy, histological type of tumour, lymphoid infiltration and vessel invasion were estimated. In this study, the potential role of SNPs of the ABCB1/MDR1 gene as a prognostic marker for CRC was analysed.Materials and methodsTumour specimens of 95 patients with CRC were studied. Using automated sequencing or PCR-RFLP method, DNA for three common SNPs of ABCB1/MDR1 was extracted and analysed. The results of genotyping and haplotype analysis with histopathological features, grading and clinical staging of neoplasms were correlated.ResultsA statistically significant higher frequency of T(1236) allele in T1/T2 (89.7%), M0 groups (81.6%) and I/II clinical staging (82.7%) in comparison with T3/T4 (68.2%), M1 groups (47.4%) and III/IV clinical staging (65.1%) was detected. Furthermore, multivariate analysis according to Cox's proportional hazard model indicated that the T(1236) allele is a good, independent prognostic factor and the presence of this allele decreases the risk of death in comparison with a group without this allele (HR = 0.26; p = 0.0424). In addition, a statistically significant higher frequency of C(3435) allele and significant differences in the C(3435) allele distribution in N1/N2 group (91.7% and 62.5%, respectively) than N0 group (71.2% and 44.9%, respectively) was found. Each of the eight possible haplotypes was noted in M0 or I/II group and only seven in M1 or III/IV group. Haplotype T(1236)-G(2677)-C(3435) only in less advanced CRC subjects (9.6% in I/II and 9.2% in M0 group) was detected. In addition, significant differences in haplotype distributions between M0 or I/II and M1 or III/IV group were found (p = 0.01 and p = 0.05, respectively).ConclusionsThese results suggest association between T(1236) allele and T(1236)-G(2677)-C(3435) haplotype and less advanced CRC, so these genetic markers may play a role as potentially good prognostic factors. Differences in haplotype distributions and degree of clinical staging may suggest that some other potential SNPs, especially in regulatory region of ABCB1/MDR1 gene, may influence P-glycoprotein function and CRC progression.

Project description:IntroductionHyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland.AimsTo investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics.MethodsIn total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone.ResultsWe did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia.ConclusionThis study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia.

Dataset Information

Genetic Polymorphisms of Multidrug Resistance Gene-1 (MDR1/ABCB1) and Glutathione S-Transferase Gene and the Risk of Inflammatory Bowel Disease among Moroccan Patients.

Publications

Genetic Polymorphisms of Multidrug Resistance Gene-1 (MDR1/ABCB1) and Glutathione S-Transferase Gene and the Risk of Inflammatory Bowel Disease among Moroccan Patients.

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