Dataset Information

Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia.

ABSTRACT:

Objective

The risk of contracting tuberculosis (TB) and the efficacy of TB therapy are affected by several factors, including genetic variation among populations. In the Indonesian population, data on the genes involved in drug transport and metabolism of TB therapy are limited. The aim of this study was to identify the genetic profile of the ABCB1 gene (rs1128503 and rs1045642) and CYP2E1 gene (rs3813867) in Indonesians with TB. This study was a cross-sectional study of 50 TB outpatients in Jambi city, Indonesia. Sociodemographic characteristics were obtained from medical records. Whole blood was collected, and genomic DNA was isolated. Single nucleotide polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism with HaeIII, MboI, and PstI for rs1128503, rs1045642 (ABCB1), and rs3813867 (CYP2E1), respectively.

Result

The frequency of alleles of each gene was analyzed by Hardy-Weinberg equilibrium. The genetic profiles of ABCB1 rs1128503 and rs1045642 were varied (CC, CT, TT), while CYP2E1 rs3813867 was present in CC (wild type). The genetic variations of ABCB1 and CYP2E1 may have no significant correlation with the duration of TB therapy. Nevertheless, this study may provide as preliminary results for the genetic profiles of ABCB1 (rs1128503, rs1045642) and CYP2E1 (rs3813867) in the Indonesia population.

SUBMITTER: Barliana MI

PROVIDER: S-EPMC8325820 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeDabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty. ABCB1 is a key gene in the metabolism of dabigatran etexilate. Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications.MethodsThe prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty. Patients with anemia and coagulation disorders, elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study. The association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a real-time polymerase chain reaction assay and laboratory blood tests. The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers. The probability of the type 1 error (p) was less than 0.05 was considered statistically significant. BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests. All calculations were performed using Rprogramming language v3.6.3.ResultsFor all polymorphisms there was no association with the level of platelets, protein, creatinine, alanine transaminase, prothrombin, international normalized ratio, activated partial thromboplastin time and fibrinogen. Carriers of rs1128503 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.015) while receiving dabigatran therapy during the postoperative period compared to the CC, CT. Carriers of rs2032582 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.006) while receiving dabigatran therapy during the postoperative period compared to the GG, GT phenotypes. These differences were not observed in carriers of rs4148738.ConclusionIt might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503 (TT) or rs2032582 (TT) polymorphisms in favor of other new oral anticoagulants. The long-term implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.

Project description:BackgroundTuberculosis (TB) has contributed to a significant disease burden and economic loss worldwide. Given no gold standard for diagnosis, early identification of TB infection has been challenging. This study aimed to comparatively investigate the prevalence of TB across diagnostic approaches (sputum AFB, sputum culture, sputum genetic test, and chest x-ray) and geographical areas of Indonesia.MethodsParticipant demographic variables and TB screening test results were obtained from the Tuberculosis Unit, Health Research and Development Agency, Ministry of Health (HRDA-MoH). The prevalence of pulmonary TB in populations aged 15 years and over was calculated using TB cases as a numerator and populations aged 15 years and over as a denominator. Variations across geographical areas and diagnostic approaches were expressed as prevalence and 95% confidence interval (CI).ResultsA total of 67,944 records were reviewed. Based on bacteriological evidence, the prevalence of TB per 100,000 in Indonesia was 759 (95% CI: 589.7-960.8) with variations across areas: 913 (95% CI 696.7-1,176.7; Sumatra), 593 (95% CI 447.2-770.6; Java-Bali), and 842 (95% CI 634.7-1,091.8; other islands). Also, the prevalence of TB varied across diagnostic approaches: 256.5 (sputum AFB), 545 (sputum culture), 752.2 (chest x-ray), and 894.9 (sputum genetic test). Based on sputum AFB, the TB prevalence varied from 216.6 (95% CI 146.5-286.8; Java-Bali), 259.9 (95% CI 184.2-335.6; other islands) to 307.4 (95% CI 208.3-406.5; Sumatra). Based on sputum culture, the TB prevalence ranged from 487.9 (95% CI 433.6-548.6; Java-Bali), 635.9 (95% CI 564.9-715.1; Sumatra), to 2,129.8 (95% CI 1,664.0-2,735.6; other islands). Based on chest x-ray, the TB prevalence varied from 152.1 (95% CI 147.9-156.3; Java-Bali), 159.2 (95% CI 154.1-164.3; Sumatra), to 864 (95% CI 809-921.4; other islands). Based on sputum genetic test, the TB prevalence ranged from 838.7 (95% CI 748.4-900.8; Java-Bali), 875 (95% CI 775.4-934.2; Sumatra), to 941.2 (95% CI 663.6-992.3; other islands).ConclusionsThe variation of TB prevalence across geographical regions could be confounded by the diagnostic approaches.Trial registrationThis study was approved by the Institutional Review Board of Chulalongkorn University (IRB No. 684/63).

Dataset Information

Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia.

Objective

Result

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