C3435T Polymorphism of the ABCB1 Gene in Polish Patients with Inflammatory Bowel Disease: A Case–Control and Meta-Analysis Study

P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn’s disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.

C3435T Polymorphism of the ABCB1 gene in the Yakut Population

Background: The ABCB1 gene is responsible for resistance to various cytotoxic drugs. The product of the ABCB1 gene, P-glycoprotein (P-gp), acts as a transmembrane pump and influences the action of many drugs. More than 40 SNPs of the ABCB1 gene that alter the expression of P-gp have been identified. The ABCB1 rs1045642 SNP, designated as C3435T (C-the wild-type allele, T-the variant allele), correlates with the activity of P-gp. The aim of our research was to study the distribution of alleles and genotypes of the ABCB1 C3435T polymorphism in Yakuts, in comparison with other human populations. Methods and Results: The studied cohort included 149 healthy Yakut volunteers (36 men and 113 women). The average age of participants was 30.67±0.06 years. The ABCB1 gene is a highly polymorphic gene; the allele frequency of the C3435T polymorphism differs widely among the studied populations. The frequency of the mutant T-allele among the Yakuts was 51% .In the studied group of Yakuts, we revealed the prevalence of the heterozygous CT genotype (75.8%). The Yakuts have a relatively low frequency of CC (10.7%) and TT (13.4%) genotypes. This preliminary study did not include the objective of proving the relationship between the ABCB1 C3435T polymorphism and addictive disorders in Yakuts. The further search for functional polymorphisms of the ABCB1 gene and associations with addictive behavior using a systematic approach on larger samples is of great practical importance.

Effects of MDR1 Gene Polymorphism on Efficacy and Hematotoxicity of Epirubicin-Based Regimen in Patients with Breast Cancer in Southwest China

Objective: To investigate the predictive value of multi-drug resistance gene (MDR1) polymorphism in the efficacy and hematological toxicity of chemotherapy regimen based on Epirubicin in patients with breast cancer in Southwest China. Methods: Patients who received Epirubicin-based chemotherapy were included, and polymorphism of C1236T, G2677T/A and C3435T were detected by time-of-flight mass spectrometry (TOF-MS). The correlation between different genotypes and chemotherapy efficacy and blood toxicity were evaluated. Results: A total of 102 patients were included, 44 of them were treated with neoadjuvant chemotherapy. There was no significant correlation between all genotypes and alleles of the three SNPs and the efficacy of neoadjuvant chemotherapy regimen containing Epirubicin in patients with breast cancer. There was a significant correlation between C3435T polymorphism and grade Ⅲ-Ⅳ leukopenia in patients with breast cancer, the incidence of grade Ⅲ-Ⅳ leukopenia in patients with C allele was significantly lower than that in patients with T allele. Conclusion: T allele of C3435T polymorphism may be a risk factor for grade Ⅲ-Ⅳ leukopenia in patients with breast cancer after chemotherapy.

Association of the ABCB1 C3435T gene polymorphism (SNPs) with the response to neoadjuvant chemotherapy in women with breast cancer in northeastern Brazil

<p><strong>Introduction</strong>: breast cancer (BC) is the most common tumor and the leading cause of cancer-related death among the female population<br />worldwide. Polymorphisms genetics of ABCB1 gene contributed to breast cancer susceptibility and interindividual differences in<br />chemotherapy response. <strong>Objectives</strong>: to evaluate the association between the ABCB1 C3435T gene polymorphism (SNPs) with the<br />response to neoadjuvant chemotherapy in women with breast cancer. <strong>Methodology</strong>: this study included 32 female patients who<br />received neoadjuvant chemotherapy. The polymorphisms were genotyped through real-time allele-specific polymerase chain reaction<br />(PCR). The statistical analysis was performed using the Fisher’s exact test or Pearson’s chi-square test in the Statistical Package for<br />Social Sciences (SPSS) version 20.0 software. <strong>Results</strong>: the genotypes found for the C3435T polymorphism were in Hardy-Weinberg<br />equilibrium and their genotypic distributions were CC= 10 (31.1%), CT= 14 (43.8%), and TT= 08 (25.0%) with χ2: 0.86 and p-value &gt;<br />0.05. Allele frequencies were C = 0.54 and T = 0.46. There were no significant statistical differences between genotypes considering the<br />response to neoadjuvant chemotherapy and immunohistochemistry; the presence of the T allele was associated with worsen axillary<br />status response to neoadjuvant chemotherapy. <strong>Conclusion</strong>: no definite association between the presence of C3435T polymorphism<br />and the response to neoadjuvant chemotherapy was observed. Further studies in Brazil involving larger samples will contribute to<br />validating the results of this study.</p>

Allele Frequency of Carbamazepine Major Efflux Transporter Encoding Gene ABCB1 C3435T among Javanese-Indonesian Population

BACKGROUND: Genetic variations in ABCB1 gene that encodes P-glycoprotein, the main transporter in the efflux of carbamazepine (CBZ) from the brain cells, can lead to pharmacodynamic and pharmacokinetic variability. Polymorphism of C3435T is widely known to cause protein overexpression that contributes to an increased risk of CBZ resistance. AIM: This study determined the allele frequency distribution of ABCB1 C3435T gene in healthy subjects of the Javanese population as a major ethnic group in Indonesia. METHODS: This cross-sectional study involved 100 healthy volunteers who fulfilled the inclusion criteria. The genotype analysis to detect polymorphism in the targets employed the polymerase chain reaction-restriction fragment length polymorphism method with 5’-TGCTGGTCCTGAAGTTGATCTGTGAAC-3’ as the forward primer and 5’-ACATTAGGCAGTGACTCGATGAAGGCA-3’ as the reverse primer. RESULTS: The frequency of subjects with C allele in ABCB1 C3435T gene reached 53%, higher than that with T allele. CONCLUSION: This finding was nearly the same as that in studies of the populations in China, Turkey, and four countries in the South European continent. It is recommended to conduct further research on the correlation between C3435T polymorphism and CBZ dose variability to provide a comprehensive approach to epilepsy management in patients receiving CBZ.

Influence of ABCB1 C3435T gene polymorphisms on tumor response to neoadjuvant chemotherapy in locally advanced breast cancer patients from Northeastern Brazil.

Background: Breast cancer (BC) is the most common tumor and the leading cause of cancer-related death among the female population worldwide. To evaluate the association between the ABCB1 C3435T single gene nucleotide polymorphisms (SNPs) with the response to neoadjuvant chemotherapy in women with breast cancer. Methods: This study included 32 female patients who received neoadjuvant chemotherapy. The polymorphisms were genotyped through real-time allele-specific polymerase chain reaction (PCR). The statistical analysis was performed using the Fisher's exact test or Pearson's chi-square test in the Statistical Package for Social Sciences (SPSS) version 20.0 software. Results: The genotypes found for the C3435T polymorphism were in Hardy-Weinberg equilibrium and their genotypic distributions were CC= 10 (31.1%), CT= 14 (43.8%), and TT= 08 (25.0%) with χ2: 0.86 and p-value > 0.05. Allele frequencies were C = 0.54 and T = 0.46. There were no significant statistical differences between genotypes considering the response to neoadjuvant chemotherapy and immunohistochemistry; the presence of the T allele was associated with worsen axillary status response to neoadjuvant chemotherapy. Conclusion: No definite association between the presence of C3435T polymorphism and the response to neoadjuvant chemotherapy was observed. Further studies in Brazil involving larger samples will contribute to validating the results of this study. Keywords: Breast cancer; Neoadjuvant Chemotherapy; Polymorphisms; Gene ABCB1