Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

Timuçin, Meryem; Alagözlü, Hakan; Özdemir, Semra; Özdemir, Öztürk

doi:10.5812/hepatmon.7522

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…The results showed similarity in the prevalence of the C allele and the T allele in the population studied, with CT being the most prevalent genotype in these patients. Among the patients with HCV infection who underwent treatment with pegylated interferon-alpha and ribavirin, our findings corroborate the results found by Timucin et al, which also showed a higher frequency for the CT genotype among these patients (25) . Some studies claim that the presence of the T allele generates no response to treatment, however we did not find such an association; furthermore, the presence of this allele is also associated with development of some type of cancers such as hepatocellular carcinoma, prostate cancer, ovarian cancer and others (28) .…”

Section: Discussionsupporting

confidence: 82%

“…The literature reports an association between the C3435T polymorphism of the MDR1 gene and various diseases. Rose et al suggest a regulatory role of MDR1 gene expression in patients with hepatopathies (24) ; other studies about this SNP have shown that the C allele is associated with a better prognosis in patients with hepatitis C and in patients with hepatocellular carcinoma (1,25) . On the other hand, in other pathological conditions such as HIV infection, the T allele appears to confer a better prognosis; HIV-infected patients homozygous for the TT genotype, when treated with HAART, have shown significant increases in CD4 cell count and better response to the treatment of hepatitis C (11,15,29) .…”

Section: Discussionmentioning

confidence: 99%

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Frequency of the Mdr1 Gene Polymorphism Rs1045642 (C3435t) in HCV-Hiv Co-Infected Patients

Marasca

Machado

Filho

et al. 2016

Arq. Gastroenterol.

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-Background -Due to the high prevalence of co-infection by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and the severity of these infections, the understanding of the biological mechanisms involved in these processes, including viral behavior and host genetic profile, is of great importance for patient treatment and for public health policies. Some single nucleotide polymorphisms (SNPs) in the human genome, such as the SNP rs1045642 (C3435T) in the MDR1 gene, have been reported to be associated to the sustained virological response (SVR) to HCV treatment in HCV-HIV co-infected patients. Objective -The present study analyzes the MDR1 gene C3435T polymorphism in HCV-HIV co-infected patients.Methods -A total of 99 HCV-HIV patients were included in the study. The DNA was extracted from blood samples, and the SNP rs1045642 was assessed by Real Time PCR (qPCR). Risk factors for acquiring the virus and the SVR after HCV treatment with pegylated interferon-alpha and ribavirin were also analyzed. Results -Among the patients, 54 (54.5%) were male and 45 (45.5%) were female. The average age was 46.1±9.8 years. The SVR after HCV treatment was 40%. The frequencies of MDR1 genotypes CC, CT and TT were 28.3%, 47.5% and 24.2%, respectively. Allele frequencies were 52% for the C allele and 48% for the T allele. No association was found for SNP rs1045642 (C3435T) regarding response to treatment (P=0.308). Conclusion -In this study, the C3435T polymorphism in the MDR1 gene appears not to be associated with SVR in HCV-HIV co-infected individuals. HEADINGS -Hepacivirus. HIV. Single nucleotide polymorphism. P-glycoprotein. Coinfection. Interferon-alpha. Ribavirin.Declared conflict of interest of all authors: none Disclosure of funding: no funding received Financial support: Marasca GS and Souza ACS hold a fellowship from CAPES (Ministry of Education, Brazil).

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Frequency of the Mdr1 Gene Polymorphism Rs1045642 (C3435t) in HCV-Hiv Co-Infected Patients

Marasca

Machado

Filho

et al. 2016

Arq. Gastroenterol.

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“…In agreement, both genetic variants of ABCG2 rs2, 231,137 (34 G > A) and rs2, 622, 604T (1143 C > T) were associated with the low sorafenib plasma levels and improved clinical outcome [35]. It is worth mentioning that genetic polymorphisms of both ABCB1 and ABCG2 in relevance to HCC susceptibility, HCC risk of recurrence following liver transplantation [53] as well as a therapeutic response [58] have been thoroughly studied which provide a solid ground for how genetic variability can implicate HCC since its incidence till therapeutic response.…”

Section: Abc Transportersmentioning

confidence: 66%

Genetic Heterogeneity, Therapeutic Hurdle Confronting Sorafenib and Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Atwa

Odenthal

Tayebi

2021

Cancers

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Despite the latest advances in hepatocellular carcinoma (HCC) screening and treatment modalities, HCC is still representing a global burden. Most HCC patients present at later stages to an extent that conventional curative options are ineffective. Hence, systemic therapy represented by the tyrosine kinase inhibitor, sorafenib, in the first-line setting is the main treatment modality for advanced-stage HCC. However, in the two groundbreaking phase III clinical trials, the SHARP and Asia-Pacific trials, sorafenib has demonstrated a modest prolongation of overall survival in almost 30% of HCC patients. As HCC develops in an immune-rich milieu, particular attention has been placed on immune checkpoint inhibitors (ICIs) as a novel therapeutic modality for HCC. Yet, HCC therapy is hampered by the resistance to chemotherapeutic drugs and the subsequent tumor recurrence. HCC is characterized by substantial genomic heterogeneity that has an impact on cellular response to the applied therapy. And hence, this review aims at giving an insight into the therapeutic impact and the different mechanisms of resistance to sorafenib and ICIs as well as, discussing the genomic heterogeneity associated with such mechanisms.

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“…23,24,26,29 It has been reported that C3435T, one of the silent polymorphisms, may be associated with ribavirin resistance in chronic hepatitis C infection. 30 In our study, we investigated whether another silent polymorphism, C1236 T, was associated with lamivudine resistance in chronic hepatitis B patients. The CT genotype (72.5%) was higher in the lamivudineresponsive group in comparison to the non-responsive group (53.8%), however, no statistical difference was noted.…”

Section: Discussionmentioning

confidence: 99%

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

Şıvgın¹,

Yılmaz²,

Rüstemoğlu³

et al. 2023

KMJ

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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<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>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.

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Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

Cited by 6 publications

References 42 publications

Frequency of the Mdr1 Gene Polymorphism Rs1045642 (C3435t) in HCV-Hiv Co-Infected Patients

Frequency of the Mdr1 Gene Polymorphism Rs1045642 (C3435t) in HCV-Hiv Co-Infected Patients

Genetic Heterogeneity, Therapeutic Hurdle Confronting Sorafenib and Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

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

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