C3435T Polymorphism Research Articles

Effect of MDR1 C3435T and CYP2C19 genetic polymorphisms on the outcome of Helicobacter pylori eradication treatment in children with gastritis and peptic ulcer, Vietnam

BackgroundHelicobacter pylori eradication therapy based on antimicrobial susceptibility in Vietnamese children currently get low efficiency. There are causes of treatment failure, among host genetic factors namely MDR1 C3435T and CYP2C19 affect the absorption and metabolism of proton pump inhibitors - a crucial component of eradication therapy. The study aimed to investigate the effect of MDR1 C3435T and CYP2C19 genetic polymorphisms on the cure rate.Methods207 pediatric patients with gastritis and peptic ulcer infecting Helicobacter pylori completed the eradication therapy based on antimicrobial susceptibility with proton pump inhibitor esomeprazole. Eradication efficacy was assessed after at least 4 weeks by the urease breath test. MDR1 C3435T genetic polymorphism and CYP2C19 genotype were determined using a sequencing method based on Sanger’s principle.ResultsAmong 207 children recruited in this study, the ratio of CYP2C19 EM, IM, and PM phenotypes was 40.1%, 46.4%, and 16.9%, respectively. The patient with MDR1 3435 C/C polymorphism accounted for 43.0%, MDR1 3435 C/T was 40.1%, and MDR1 3435T/T was 16.9%. The cure rate of Helicobacter pylori infection in patients with CYP2C19 EM genotype was 78.3%; 83.3% of those with the IM genotype, and PM genotype was 96,4% (p = 0.07). Successful eradication rates for Helicobacter pylori were 85.4%, 86.7%, and 68.6% in patients with the MDR1 3435 C/C, C/T, and T/T, respectively (p = 0.02). Multiple logistic regression analysis found that MDR1 C3435T genetic polymorphisms of patients were significant independent risk factors for treatment failure, and CYP2C19 genotype did not affect Helicobacter pylori eradication.ConclusionsThe Helicobacter pylori eradication rates by regimens based on antibiotic susceptibility and esomeprazole were not significantly different between the CYP2C19 phenotypes. The MDR1 C3435T polymorphism is one of the factors impacting Helicobacter pylori eradication results in children.

The association between abcb1 gene polymorphism and clopidogrel response variability in stroke ischemic: a cross sectional study

BackgroundClopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency.MethodsA cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020 and 2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (> 208 PRU), responsive (95–208 PRU), and bleeding risk (< 95 PRU).Results124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk. ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p = 0,008; 95%CI 1,41 − 10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively.ConclusionABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of ABCB1 C1236T was homozygote variant; while for ABCB1 C3435T was heterozygote.

ABCB1 C1236T, G2677TA and C3435T Genetic Polymorphisms and Antidepressant Response Phenotypes: Results from a Portuguese Major Depressive Disorder Cohort.

P-glycoprotein (P-GP) is a transporter molecule expressed on the apical surface of capillary endothelial cells of the Blood-Brain Barrier (BBB), whose activity heavily influences drug distribution, including antidepressants. This transporter is encoded by ABCB1 gene, and genetic variations within ABCB1 gene have been proposed to affect drug efflux and have been previously associated with depression. In this context, we aimed to evaluate the role of C1236T, G2677TA and C3435T ABCB1 genetic polymorphisms in antidepressant treatment phenotypes from a cohort of patients harboring Major Depressive Disorder. Patients enrolled in the study consisted of 80 individuals with Major Depressive Disorder, who took part in a 27-month follow-up study at HML, Portugal. To investigate the correlation between ABCB1 polymorphisms and antidepressant response phenotypes, DNA was extracted from peripheral blood, and C1236T, C3435T and G2677TA polymorphisms were genotyped with TaqMan® SNP Genotyping Assays. Despite the fact that the evaluated polymorphisms (C1236T, C3435T and G2677TA) were not associated with treatment resistant depression, or relapse, we observed that patients carrying TT genotype of the C3435T polymorphism remit earlier than the ones carrying CC or CT genotypes (10.2 weeks vs. 14.9 and 21.3, respectively, p = 0.028, Log-rank test). Since we found an association with C3435T and time to remission, and not to the absence of remission, we suggest that this polymorphism could have an impact on antidepressant drug distribution, and thus influence on the time to remission will occur, without influencing the risk of remission itself.

Association between the MDR1 rs1045642 polymorphism and breast cancer risk: An updated meta‑analysis.

Multidrug resistance 1 (MDR1) is a transmembrane transporter on the cell membrane. As an ATP-dependent efflux pump, MDR1 is mainly responsible for the adsorption, distribution, metabolism, excretion and transportation of anticancer drugs to cancer cells. Mutations of the MDR1 gene may be associated with the incidence of cancer. In the past decade, associations found between the MDR1 rs1045642 polymorphism and breast cancer have been inconsistent and inconclusive. Therefore, the present study performed a meta-analysis including studies published up until August 16, 2023 to systematically evaluate the association between the MDR1 rs1045642 polymorphism and breast cancer risk. A total of 21 published case studies involving 6,815 patients with breast cancer and 9,227 healthy participants were included in the meta-analysis. Overall, the MDR1 rs1045642 polymorphism was not significantly associated with breast cancer-associated risk. However, in the subgroup analysis, the MDR1 rs1045642 polymorphism was found to be notably associated with a higher risk of breast cancer among Asian populations in recessive models [TT vs. CT + CC; odds ratio (OR)=1.393; 95% confidence interval (CI), 1.143-1.698; P=0.001; I2<25%]. The MDR1 C3435T polymorphism was also associated with a notable decrease in the incidence of breast cancer in mixed ethnicity populations (TT and CT + CC; OR=0.578; 95% CI, 0.390-0.856; P=0.006; I2<25%). In Caucasian populations, the MDR1 rs1045642 polymorphism was not associated with breast cancer risk. In conclusion, the present meta-analysis demonstrated that the MDR1 rs1045642 polymorphism may increase the risk of breast cancer in Asian populations, is associated with a reduced risk of breast cancer in mixed populations but has no notable effect in Caucasian populations.

NeuroPredict: study of the predictive value of ABCB1 genetic polymorphisms and associated clinical factors in chronic chemotherapy-induced peripheral neuropathy (CIPN).

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common entity (30%-40%) and can significantly limit the quality of life of patients, especially those that persist for more than 6months after treatment (chronic neuropathy). Studies have shown a possible association between the presence of genetic polymorphisms in ABCB1 and the development of acute CIPN, although this relationship with chronic CIPN remains unexplored. This is an analytical observational case-control study defined by the presence (cases) or absence (controls) of CIPN at 6 months after the end of the neurotoxic drug. Our aim is to demonstrate whether these ABCB1 polymorphisms also influence the chronification of this toxicity, as well as the clinical factors that can help us to predict it. Methods: The study included 152 patients treated with tri-weekly oxaliplatin (O) or weekly paclitaxel (P); 86 cases and 66 controls. Clinical and analytical parameters were analysed including the study of ABCB1 genetic polymorphisms in a blood sample. Results: ABCB1 genetic polymorphisms C1236T (rs1128503) and C3435T (rs1045642) are associated with the development of chronic CIPN in patients treated with P. No differences were found in patients treated with O. Other predictive factors to be considered in the development of this toxicity are age >60 years, BMI ≥30, toxic habits and cardiovascular risk factors. Conclusion: CIPN is a common and understudied toxicity, despite being a limiting factor in the quality of life of many patients. As described in acute CIPN, our study demonstrates the relationship between chronic neuropathy and being a carrier of specific polymorphisms (C1236T and C3435T) of the ABCB1 gene in patients treated with P. In addition, there are modifiable factors (obesity, smoking, or alcohol) that may influence its development. Further prospective studies are needed to investigate genetic and clinical modifiable factors predisposing to CIPPN to develop prevention and treatment strategies.

Multidrug resistance Gene-1 polymorphisms (C3435T and G2677T) and the risk of inflammatory bowel disease in Egyptian patients

Background and study aimsThe multidrug resistance 1 (MDR1) gene is a gene involved in the pathogenesis of inflammatory bowel disease (IBD).The aim of the study is to investigate the association of MDR-1 gene polymorphisms (C2345T and G2677T) and IBD incidence in Egyptian patients, and its relation with disease severity. Patients and methodsThis is a case-control study where genotyping of MDR-1 gene C3435T and G2677T single nucleotide polymorphisms (SNPs) were assayed. ResultsForty naïve IBD patients, who were composed of 25 UC and 15CD, were compared to 60 healthy controls. They were young aged with significant female predominance, particularly in CD (P = 0.004). UC was mainly (48 %) presented in moderate severity while CD was mainly (53.3 %) presented with mild severity. MDR-1 gene C3435T SNP was not statistically related to IBD, whether in terms of genotypes or alleles, yet its T allele was significantly related to moderate cases of UC (P = 0.014). However, GG genotype of G2677T SNP was significantly low in IBD (P = 0.013), while TT genotype and T allele were significantly related to CD (P = 0.011, and 0.012 respectively). Moreover, G allele proved to be associated significantly with moderate cases of UC (P = 0.001) and mild cases of CD (P = 0.002). ConclusionsMDR-I gene G2677T SNP GG genotype proved to be protective against IBD, thus may be considered in diagnostic workup of IBD including its severity.

Correlation between gene polymorphism and adverse reactions of high-dose methotrexate in osteosarcoma patients: a systematic review and meta-analysis

ObjectiveWe aimed to provide a reference based on evidence for an individualized clinical medication of high-dose methotrexate (HD-MTX) in osteosarcoma patients by evaluating the effect of gene polymorphism on adverse reactions of HD-MTX usage.MethodsSeveral databases were combed for research on the association between gene polymorphisms and adverse reactions to HD-MTX up to January 2023. A meta-analysis and/or descriptive analysis on the incidence of HD-MTX-related adverse reactions were conducted by using clinical studies meeting inclusion criteria.ResultsTwelve studies involving 889 patients were included. There were 8, 6, 5, and 4 studies related to MTHFR C677T, MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphisms, respectively. The results of the meta-analysis showed that the MTHFR C677T polymorphism was associated with G3-4 hepatotoxicity, G3-4 nephrotoxicity, G3-4 gastrointestinal toxicity, and G3-4 mucositis under the recessive genetic model (MM vs. Mm/mm). Limited research showed that MTHFR C677T was associated with G3-4 nephrotoxicity in the allelic genetic model (M vs. m). MTHFR A1298C polymorphism was associated with a decreased risk of adverse reactions to HD-MTX usage, without statistical significance. This review's descriptive analysis showed no significant correlation between the RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions of HD-MTX.ConclusionThe MTHFR C677T mutation may enhance the risk of HD-MTX adverse reactions in osteosarcoma patients. Existing studies have not found a significant correlation between the MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions caused by HD-MTX. Lastly, this conclusion was limited because of few studies.

Prevalence of genetic polymorphisms ABCB1/ C3435T in patients with epilepsy in Iranian population

Introduction: Epilepsy is a common neurological disorder affecting approximately 1% of the global population. A significant proportion of patients develop drug-resistant epilepsy (DRE), which leads to poor outcomes for treatments and low quality of life. The multidrug transporter P-glycoprotein, encoded by the ABCB1 gene, plays a key role in limiting brain penetration of antiepileptic drugs. The C3435T single nucleotide polymorphism (SNP) in ABCB1 has been linked to variable P-glycoprotein expression and AED response. In this study, the prevalence of C3435T genotypes among epilepsy patients and healthy controls in Fars Province, Iran was investigated. Materials and methods: This study involved 50 patients diagnosed with epilepsy and 100 healthy individuals without a history of seizures or epilepsy. Genotyping was conducted using PCR-RFLP analysis. Results: The variant T allele occurred at a frequency of 52% in cases and 54% in controls. However, no significant association between the C3435T polymorphism and epilepsy risk was observed. Interestingly, it was found that the CT genotype was overrepresented in drug-responsive patients compared to those with drug-resistant cases. This suggests that individuals with the CT genotype may have a more favorable response to antiepileptic drug therapy. Conclusion: These findings suggest that the ABCB1 C3435T variant may play a role in influencing seizure control specifically among Iranian patients, but its effects on susceptibility are minimal. Moreover, individuals with the CT genotype may have a more favorable response to antiepileptic drug therapy. Further research involving larger cohorts is needed to fully understand the impact of ABCB1 genetics on determining individual responses to antiepileptic drugs. Such research could also pave the way for personalized management strategies based on pharmacogenomic testing.

The ABCB1 C3435T Polymorphism is Associated with Triglyceride Reduction in Atorvastatin-treated Uygur Patients with Coronary Heart Disease and Dyslipidemia: An Observational Study.

The morbidity of coronary heart disease (CHD) and dyslipidemia in the Uygur population of Xinjiang is higher than the national average. Interindividual variability of the response to atorvastatin is a major clinical problem; generally, statins shed less impressive benefits for females than males. Nevertheless, it is unclear whether ABCB1 genes and sex modify the efficacy of atorvastatin in Uygur patients. To determine the impact of ABCB1 gene polymorphisms on the therapeutic response to atorvastatin in a Uygur population with dyslipidemia. Patients with dyslipidemia were treated with 20 mg/d or 40 mg/d atorvastatin for two to six months. TC, LDL-C, HDL-C, TG, APOB, APOE, LP(a), and APOA1 levels were measured before and after atorvastatin administration. We performed genotyping of ABCB1 C3435T and G2677T variants using hybridization sequencing. The association of variants between the percentage of change in TG levels was examined using multiple linear regression analysis. We enrolled 193 Uygur patients. Atorvastatin reduced TG, LDL-C, TC, APOB, and APOE levels (P < 0.05), whereas LP(a) and APOA1 levels increased (P < 0.05). In multiple linear regression analysis, baseline TG level (beta 0.204; 95% confidence interval (CI): 1.980-10.493; P = 0.004) and TT genotype of ABCB1 C3435T (beta 0.162; 95% CI: 2.517-23.406; P = 0.023) predicted TG reduction with atorvastatin therapy in overall patients. Baseline TG level (beta 0.346; 95% CI: 4.374 -13.34; P < 0.001) with the TT genotype of ABCB1 C3435T (beta 0.401; 95% CI: 4.053-28.356; P = 0.021) was associated with a significant reduction in TG levels in men. Only baseline TG level predicted TG reduction within six months of atorvastatin therapy for females (beta 0.61; 95% CI: 3.204-20.557; P = 0.041). In patients with the ABCB1 C3435T TT genotype, atorvastatin more effectively lowered TG than other polymorphisms. This investigation may provide insights into effective individualized therapies for CHD and dyslipidemia in the Uygur population.

The Effect of the ABCB1(MDR-1) C3435T Polymorphism in Turkish Patients with Aspirin Resistance in Acute Ischemic Stroke.

Recurrence of thrombotic events during aspirin therapy is known as aspirin resistance (AR). This study aimed to investigate the rate of AR, the factors influencing AR in patients with acute ischemic stroke under regular aspirin use, and the relationship between AR and ABCB1 (MDR-1) C3435T (rs1045642) polymorphism. Throughout this multicenter prospective study, 174 patients with acute ischemic stroke who had been prescribed aspirin for at least one month due to the risk of vascular disease, along with 106 healthy volunteers, were included as part of the study group. The results of our study indicate that AR was detected in 21.3% of the patient group. According to the results of an analysis of the polymorphism of the ABCB1 C3435T in patients with AR compared to those with aspirin sensitivity, patients with AR possessed more heterozygous (CT) and homozygous genotypes (TT) than those with aspirin sensitivity (p = 0.001). Based on multivariate logistic regression analysis of factors affecting AR in acute ischemic stroke patients, hypertension (OR: 5.679; 95% CI: 1.144-28.19; p = 0.034), heterozygous (CT) genotype (OR: 2.557; 95% CI: 1.126-5.807; p = 0.025), increased platelet values (OR: 1.005; 95% CI: 1.001-1.009; p = 0.029), and CRP/albumin values (OR: 1.547; 95% CI: 1.005-2.382; p = 0.047) were found to be associated with a greater risk of AR. The presence of heterozygous (CT) genotype in the ABCB1 C3435T gene region in the Turkish population is associated with an increased risk of AR. When planning aspirin therapy, it is crucial to consider the ABCB1 (MDR-1) C3435T polymorphism.

ABCB1 Gene Polymorphisms Are Closely Associated With Drug-Resistant Epilepsy: Evidence Based on 377 Subjects in Chinese Pediatric Patients.

P-glycoprotein plays a role in drug resistance of epileptic patients by limiting gastrointestinal absorption and brain access to antiseizure medications. This study aimed to evaluate the association between ABCB1 polymorphisms and drug resistance in epileptic pediatric patients. Three hundred seventy-seven epileptic pediatric patients were treated with antiseizure medications and subsequently divided into the drug-responsive group (n = 256, 68%) and drug-resistant group (n = 121, 32%). The genomic DNA of patients in the different groups was extracted, followed by the determination of the ABCB1 gene polymorphisms using polymerase chain reaction-fluorescence staining in situ hybridization. Drug-resistant patients significantly exhibited a combined generalized and focal onset than drug-responsive patients (χ2 = 12.278, P < 0.001). The TT (χ2 = 5.776, P = 0.016) genotypes of G2677T and CT (χ2 = 6.165, P = 0.013) and TT (χ2 = 11.121, P = 0.001) genotypes of C3435T were significantly more frequent in drug-resistant patients than drug-responsive patients. Similarly, the GT-CT diplotype was significantly more frequent in drug-resistant patients than in drug-responsive patients. Our study findings suggest that the ABCB1 G2677T and C3435T polymorphisms are significantly associated with drug resistance in epileptic patients.

Multidrug resistant 1 (MDR1) C3435T and G2677T gene polymorphism: impact on the risk of acute rejection in pediatric kidney transplant recipients

BackgroundTacrolimus is the backbone drug in kidney transplantation. Single nucleotide polymorphism of Multidrug resistant 1 gene can affect tacrolimus metabolism consequently it can affect tacrolimus trough level and incidence of acute rejection. The aim of this study is to investigate the impact of Multidrug resistant 1 gene, C3435T and G2677T Single nucleotide polymorphisms on tacrolimus pharmacokinetics and on the risk of acute rejection in pediatric kidney transplant recipients.MethodsTyping of Multidrug resistant 1 gene, C3435T and G2677T gene polymorphism was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for 83 pediatric kidney transplant recipients and 80 matched healthy controls.ResultsIn Multidrug resistant 1 gene (C3435T), CC, CT genotypes and C allele were significantly associated with risk of acute rejection when compared to none acute rejection group (P = 0.008, 0.001 and 0.01 respectively). The required tacrolimus doses to achieve trough level were significantly higher among CC than CT than TT genotypes through the 1st 6 months after kidney transplantation. While, in Multidrug resistant 1 gene (G2677T), GT, TT genotypes and T allele were associated with acute rejection when compared to none acute rejection (P = 0.023, 0.033 and 0.028 respectively). The required tacrolimus doses to achieve trough level were significantly higher among TT than GT than GG genotypes through the 1st 6 months after kidney transplantation.ConclusionThe C allele, CC and CT genotypes of Multidrug resistant 1 gene (C3435T) and the T allele, GT and TT genotypes of Multidrug resistant 1 gene (G2677T) gene polymorphism may be risk factors for acute rejection and this can be attributed to their effect on tacrolimus pharmacokinetics. Tacrolimus therapy may be tailored according to the recipient genotype for better outcome.

The effects of MDR-1 gene polymorphisms on the clinical course of chronic hepatitis B infection

Aims: Chronic HBV infection is associated with high morbidity and mortality rate due to increased risk of hepatic cirrhosis and hepatocellular cancer. Treatment modilities and resistance is currently investigated. Several mechanisms were underlying in drug resistance. P-glycoprotein (P-gp), the product of multidrug resistance gene (MDR-1), is well-known mechanism of MDR phenotype. MDR gene C1236T polymorphism is associated with decreased p-gp function. The mutation of MDR gene can affect the clinical course of disease and response rate to treatment. It was aimed to investigate the relationship between MDR gene polymorphism and clinical course and treatment responses in chronic HBV infection in our study. Methods: A total of 90 (male/female:69/21) patients with chronic HBV infection under Lamivudine treatment was enrolled in this study. Mean ages were 49.8±12.6 (range:22-75) years. The patients were categorized as: Treatment responded (group 1: HBV-DNA is negative at 24th week) and treatment refractory (group 2: HBV-DNA is still positive after 24th week). Group 1 was consisted of 51 (M/F: 38/13) and group 2 was consisted of 39 (M/F: 31/9) patients. There was no significant difference between ages and genders of two groups. Histologic activity indexes (HAI), total bilirubin, AST and ALT levels, HBV-DNA titers were significantly higher in the patients in group 2 than group 1 (p&lt;0.05). Results: Genotype distributions; homozygous CC genotype was in 8 (15.7%),heterozygous CT genotype was in 37 (%72.5), homozygous TT genotype wasin 6 (11.8%) in patients at group 1. Homozygous CC genotype was in 13 (33.3%), heterozygous CT genotype was in 21 (53.8%), homozygous TT genotype was in 5 (12.8%) in patients at group 2. CC genotype was more common in group 2 than group 1 (p=0.044). C and T alleles’ frequencies in the group 1 and 2 were 51.96% and 60.26%, 48.04% and 39.74%, respectively (p&gt;0.05). The patients with YMDD mutation positive at group 2 (n:11), 5 (45%) had have CC genotype, 5 (45%) had have CT, 1 (9%) had have TT genotype.The patients with YMDD mutation negative at group 2 (n:8), 3 (37%) patients had have CC and 5 (63%) patients had have CT genotype. CC genotype was more common in the patients with YMDD mutation positive than group 1 (p=0.043). Moreover, CC genotype was more common in the patients with HBV-DNA positive at 12nd month of Lamivudine treatment than group 1 (p=0.042). Conclusion: Consequently; MDR-1 and p-gp polymorphisms are important factors in the clinical course of chronic HBV infection and may influence the treatment responses. In the current study, it was found that the CC genotype of MDR-1 gene C1236T was more common in the patients with lamivudine resistant HBV infection.

Role of MDR1 Gene Polymorphisms in Human Male Infertility: A Meta-Analysis.

The present meta-analysis is performed to determine the association of C1236T and C3435T polymorphisms in the MDR1 gene. Google Scholar, PubMed, and Science Direct were searched. A total of 47 studies were retrieved, of which only three case-control studies, consisting of 490 cases and 423 controls, met the selection criteria. Odds ratios (ORs) for MDR1 C1236T were as follows: Allelic model (T vs. C): OR = 1.06 [0.83, 1.35]; Additive model (TT vs. CC): OR = 0.91 [0.53, 1.56]; Dominant model (TT+CT vs. CC): OR = 0.83 [0.55, 1.24]; and Recessive model (TT vs. CT+CC): OR = 1.43 [0.95, 2.17]. However, for MDR1 C3435T: Allelic model (T vs. C): OR = 1.06 [0.83, 1.35]; Additive model (TT vs. CC): OR = 1.18 [0.75, 1.88]; Dominant model (TT+CT vs. CC): OR = 1.42 [0.99, 2.04]; and Recessive model (TT vs. CT+CC): OR = 0.90 [0.61, 1.33]. None of the four models presented a significant association of either polymorphism with the risk of infertility in men (p >.05). The present study indicates that MDR1 gene polymorphisms might not be a risk factor for male infertility. Further studies with a larger sample size are needed to be conducted to confirm the findings of the present study.

Effect of common OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 polymorphisms on perioperative analgesic and propofol demands on patients subjected to thyroidectomy surgery

BackgroundPerioperative anesthetic and/or analgesic demand present considerable variation, and part of that variation appears to be genetic in origin. Here we investigate the impact of common polymorphisms in OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 genes, on the intra-operative consumption of remifentanil and propofol, as well as the postoperative analgesic needs, in patients subjected to thyroidectomy surgery.MethodsWe conducted a prospective cohort study with 90 patients scheduled to undergo elective thyroidectomy, under total intravenous anesthesia achieved by target control infusion (TCI) of propofol and remifentanil. Postoperative analgesics were administered by protocol and on-demand by the individual patient. Genotyping was established by PCR–RFLP methods. Genotyping data, intra-operative hemodynamics, and total consumption of remifentanil and propofol, as well as postoperative analgesic needs and pain perception, were recorded for each individual.ResultsPatients with the ABCB1 3435TT genotype appeared to experience significantly less pain within one hour post-operatively, compared to C carriers [mean VAS (SD) = 0.86 (1.22) vs. 2.42 (1.75); p = 0.017], a finding limited to those seeking rescue analgesic treatment. Intra-operatively, homozygotes patients for the minor allele of OPRM1 A118G and CYP2B6 G516T appeared to consume less remifentanil [mean (SD) = 9.12 (1.01) vs. 13.53 (5.15), for OPRM1 118GG and A carriers] and propofol [median (range) = 14.95 (11.53, 1359.5) vs. 121.4 (1.43, 2349.4), for CYP2B6 516TT and G carriers, respectively] but the difference was not statistically significant in our sample.ConclusionsThe ABCB1 C3435T polymorphism appears to affect the postoperative perception of surgical pain among patients with low pain threshold. The small number of minor allele homozygotes for the OPRM1 A118G and CYP2B6 G516T polymorphisms precludes a definitive conclusion regarding the inclusion of the latter in a TCI-programming algorithm, based on the results of this study.Clinical trial registration numberACTRN12616001598471.

Multidrug Resistance-1 C3435T Polymorphism and Carbamazepine Plasma Level in Indonesian Temporal Lobe Epilepsy Patients.

Temporal lobe epilepsy (TLE) has the highest probability of becoming resistant. One of the causes was Polymorphism in multidrug resistant-1 (MDR1) C3435T. In Dr. Cipto Mangunkusumo Hospital, potential drug-resistant epilepsy prevalence was 84.51%; 66.6% of them used carbamazepine (CBZ) as antiseizure medication. This comparative cross-sectional study aimed to investigate MDR1 C3435T polymorphism and CBZ plasma level (plCBZ) in Indonesian TLE patients. TLE patient was selected consecutively; divided into drug-responsive (DRV) and drugresistant (DRE) groups. Healthy subjects were included as a control for the gene polymorphism comparison. MDR1 was identified using the restriction fragment length polymorphism PCR technique; C allele at 159 and 57bp while T allele at 216bp. High-performance liquid chromatography was used to determine plCBZ. There were 86 subjects; 61 in the study group and 25 controls. The genotype distribution between them was 0.58 vs 0.42, x2=0.54, p=0.000. In the study group, CBZ within therapeutic doses (dCBZ) had outreached the therapeutic plCBZ and found similar in all genotypes. DRE criteria were found in 37 subjects. Distribution of C and T in DRV was 0.63 vs 0.37, x2=10.4; and DRE 0.55 vs 0.45 x2=6.17 (p=0.019). In Tukey's multiple comparison post hoc test, CT in DRV had significantly lower dCBZ (330,36 ± 174,91 mg) and plCBZ (7.15 ± 2.64 mcg/mL) compared to all genotypes in DRE. Whereas mean dCBZ was around 800mg and plCBZ outreached the toxic level; TT was the highest. The genotype MDR1 distribution was similar in the normal population and DRE. Therapeutic plCBZ was achieved using the low dose. CT genotype responds to lower dCBZ, while TT genotype outreached the highest toxic plCBZ.

A meta-analysis and experimental data for multidrug resistance genes in breast cancer.

Increasing trend of breast cancer incidence worldwide is a known fact. This curable disease may become fatal if drug resistance is developed leading to metastatic cancerous tissue. This is a two parts study; a meta-analysis exploring association of drug resistance (mdr1 and ABCG2) genes with breast cancer and mutational association with molecular subtypes of cancer. Methods: PCR-SSCP for genomic polymorphisms and RT-PCR for expression analysis were performed. C3435T polymorphism of mdr1 gene was most commonly studied mutation with contradictory results. Association of ABCG2 gene mutations with untreated breast cancer was reported only by one study so far. Regarding current genomic analysis of mdr1 gene, three novel mutations were found in exon 12 and 2 mutations were found in exon 26. In ABCG2 gene, addition of C and T were found in intron 8 at the intron-exon junction. A positive correlation was observed between these mutations and tumor grade. Levels of mRNA expression revealed that they were over expressed in cancerous tissues compared with controls. These findings suggest that these genes are associated with breast cancer.

Clinical and molecular genetic parallels of steroid resistance of acantholytic pemphigus

The problem of pharmacological resistance is becoming a challenge for doctors of all specialties, especially for people suffering from severe chronic diseases, which lead to disability and death consequences, which are patients on acantholytic pemphigus (AP), who have to take system glucocorticosteroids (SGCS) for a long term. Among the existing hypotheses of formation of steroid resistance (SR) is perspective study of genetic factors, which are one of the main mechanisms of occurrence of resistance and can be connected with the alleles polymorphism of gene of multidrug resistance (MDR1). The increased expression of this gene leads to the acceleration of the elimation of drugs from cells. The study of molecular genetic peculiarities of SR in patients with AP has not been carried out until now. Thus, the study of polymorphism of MDR1 gene in patients with AP is relevant. The aim. Study the frequency of polymorphism of marker C3435T in gene MDR1 in the relationship with clinical and anamnestic peculiarities of the AP course. Materials and methods. Under the supervision were 33 patients on the AP aged from 29 to 73 years, treated in the dermatological department of the SE "IDV NAMS of Ukraine". The buccal epithelium obtained by scraping mucosa of the oral cavity was examined. The polymorphism of the C3435T marker in the MDR1 gene was determined by the PCR method. The clinical and anamnestic features of patients on AP were evaluated on a specially developed scale. Discussion. The results of the study showed clinical-anamnestic signs of lack of sensitivity to SGCS, which correlated with the results of MDR1 gene expression. The presence in patients with AP in the CT haplotype of the T allele gives reason to classify the group of patients with AP with an index of resistance (IR) as SGCS 7.3 ± 0.6 as a risk group for the development of SR. Conclusion. According to the results of the study in patients with AP, the correlation of clinical-anamnestic signs of SR with the results of gene expression was established MDR

Impact of ABCB1 C3435T Polymorphism on Treatment Response of Vitamin K Antagonists: A Systematic Review and Meta-analysis

Impact of ABCB1 C3435T Polymorphism on Treatment Response of Vitamin K Antagonists: A Systematic Review and Meta-analysis

Effect of hepar-protecting Wuzhi capsule on pharmacokinetics and dose-effect character of tacrolimus in healthy volunteers.

Wuzhi capsule (WZC), a preparation of Fructus Schisandra sphenanthera extract, has been used widely for the treatment of viral and drug-induced hepatitis in China. This study aimed to determine the pharmacokinetic parameters of tacrolimus (TAC) when co-administered with WZC and the dose-effect of WZC on tacrolimus in healthy volunteers. The effect of an increased dosage of WZC (1, 2, 6, and 8 capsules once daily) on the relative oral exposure of tacrolimus was assessed to explore the dose-response relationship between WZC and tacrolimus using bioanalysis, pharmacokinetic, and genotypical analyses. The influence of CYP3A5 and MDR1 genetic polymorphisms on the WZC dose was elucidated by maintaining the Ctrough of tacrolimus in Chinese healthy volunteers. When co-administered with WZC, the Tmax of tacrolimus was increased significantly while the apparent oral clearance was decreased. The plasma tacrolimus level in volunteers with high CYP3A5 expression was much lower than that in those with mutant CYP3A5. However, polymorphisms of MDR1 exon26 C3435T, exon21 G2677T/A, and exon12 C1236T were not associated with plasma tacrolimus levels. Our findings provide important information on interactions between modern medications and herbal products, thus facilitating a better usage of tacrolimus in patients receiving WZC.