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Home > Mutational Study of Ns5a Gene in Therapy Resistant Patients Infected With Hepatitis C Genotype 3

Mutational Study of Ns5a Gene in Therapy Resistant Patients Infected With Hepatitis C Genotype 3

Thesis Info

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Author

Shaikh, Naila

Program

PhD

Institute

Liaquat University of Medical and Health Sciences

City

Jamshoro

Province

Sindh

Country

Pakistan

Thesis Completing Year

2016

Thesis Completion Status

Completed

Subject

Molecular Biology

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/14122/1/Naila_Shaikh_Molecular_Biology_2016_HSR_LUMHS_Jamshoro_22.08.2016.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726740100

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Hepatitis C is wide spread infectious disease, affecting almost 185 million people worldwide. It is more prevalent in developing and third world countries, where people have poor health facilities and related education. In Pakistan, nearly 10 million people are affected with HCV and majority of the patients belong to poor class with limited resources for treatment. The available conventional therapy for HCV is not 100% successful and almost 50% patients fail to achieve sustained virological response. The rate of treatment response depends on genetic components of virus and host. The aim of this study was to analyze the host and viral genetic variations associated with interferon and ribavirin therapy in chronic hepatitis C patients. Genetic changes in ISDR and PKRBD region of NS5A gene of HCV and variations of human immune gene IL28B were studied in relation with response to HCV treatment. Total of 220 HCV patients, were enrolled, 100 were responders and 120 were non responders to conventional therapy. The whole blood samples were collected for viral RNA and human DNA extraction. HCV genotype was successfully determined in 60% non-responder patients The viral genomic segments were directly sequenced while IL28B SNPS were analyzed by RFLP. The results showed multiple mutations in ISDR and PKRBD regions of NS5A gene, including two consistent missense variants, A2252V and F2252I. In 74.2% (52/75) of the patients, more than 30 mutations were found in the regions. RFLP analysis of IL28B SNPS revealed that rs12980275 AA (p<0.0001), rs12979860 CT (p=0.001) and rs8099917 TT (p=0.032) genotypes are associated with response to treatment where as AG/GG genotype of rs12980275, CC/TT of rs12979860 and GT/GG of rs8099917 are associated with non response to treatment. The un-typed HCV genotypes were further explored by sequencing 5’UTR region and various nucleotide changes were observed. The results revealed the significant association of rs12980275 polymorphism with treatment response in HCV patients followed by rs12979860 and rs8099917 and various mutations in NS5A gene showed impact on treatment response. These finding may help to predict the response to treatment with IFN in HCV patients and may reduce the side effects and cost of treatment in predicting non-responder patients.
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