Study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in Malay male drug abusers

Chronic hepatitis C virus (HCV) infection is one of the major causes of liver cirrhosis and carcinoma. The underlying pathophysiology may be due to variations in immunomodulatory cytokine activities rather than the direct action of the virus itself. The objectives of this study were to investigat...

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Main Author:	Noh, Che Ismail Che
Format:	Thesis
Language:	English
Published:	2023
Subjects:	R Medicine RC109-216 Infectious and parasitic diseases
Online Access:	http://eprints.usm.my/59784/1/CHE%20ISMAIL%20BIN%20CHE%20NOH%20-%20FINAL%20THESIS%20P-UD001318%28R%29-E.pdf
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spelling	my-usm-ep.597842024-02-13T08:27:17Z Study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in Malay male drug abusers 2023-09 Noh, Che Ismail Che R Medicine RC109-216 Infectious and parasitic diseases Chronic hepatitis C virus (HCV) infection is one of the major causes of liver cirrhosis and carcinoma. The underlying pathophysiology may be due to variations in immunomodulatory cytokine activities rather than the direct action of the virus itself. The objectives of this study were to investigate the serum levels and gene expression of cytokines and the possible association of cytokine gene polymorphism on susceptibility to hepatitis C infection in Malay Male drug abusers. The selection of the subjects provides novel knowledge in understanding the high occurrence of chronic HCV among drug abusers, a vulnerable and often neglected group of patients. Interleukin-10 (IL-10) rs1800896 and rs1800871, interleukin 6 (IL-6) rs1800795, tumour necrosis factor (TNF)-α rs1800629 and tumour growth factor (TGF)-β1 rs1800471 have been selected for the investigations representing anti and proinflammatory cytokines. A total of 162 subjects were enrolled from various health clinics in Kelantan, Malaysia, and divided into two groups: 76 patients with chronic HCV infection (HP) and 86 control group (HS). The gene polymorphisms were detected through multiplex polymerase chain reaction (PCR), gene expressions by real-time reverse transcriptase polymerase chain reaction (RT-PCR), and the serum cytokine levels were measured by immunoassay. There were significant differences in the frequencies of genotype for IL-10 rs1800896 (p = 0.0422), IL-10 rs1800871 (p = 0.0498), and at the allelic level for IL-10 rs1800896 A versus G allele (p = 0.0142), TGF-β1 rs1800471 (p = 0.0051) and at the allelic level for TGF-β1 rs1800471 G versus C allele (p = 0.0082) in the HP group and the control group. The study discovered a significant difference in gene expression for TNF-α (p = 0.0328) and in the mean serum levels of IL-6, and TGF-β1 in the HP group compared to the HS group (p = 0.0180 and p = 0.0005, respectively). These findings suggest significant associations between gene polymorphisms for IL-10 rs1800896, IL-10 rs1800871, TGF-β1 rs1800471 and susceptibility to HCV infection among Malay male patients with chronic HCV infection. Gene expression of TNF-α and serum expression of IL-10, IL- 6 and TGF-β1 shows a significant association with chronic HCV infection. This study provides a novel insight into the role of cytokines and genetic variation on susceptibility to chronic HCV infection among Malay male drug abusers, discovering potential genetic and serum biomarkers for the disease, and eventually towards precision medicine for chronic HCV infection, particularly for drug abusers. 2023-09 Thesis http://eprints.usm.my/59784/ http://eprints.usm.my/59784/1/CHE%20ISMAIL%20BIN%20CHE%20NOH%20-%20FINAL%20THESIS%20P-UD001318%28R%29-E.pdf application/pdf en public phd doctoral Universiti Sains Malaysia Pusat Pengajian Sains Kesihatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R Medicine RC109-216 Infectious and parasitic diseases
spellingShingle	R Medicine RC109-216 Infectious and parasitic diseases Noh, Che Ismail Che Study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in Malay male drug abusers
description	Chronic hepatitis C virus (HCV) infection is one of the major causes of liver cirrhosis and carcinoma. The underlying pathophysiology may be due to variations in immunomodulatory cytokine activities rather than the direct action of the virus itself. The objectives of this study were to investigate the serum levels and gene expression of cytokines and the possible association of cytokine gene polymorphism on susceptibility to hepatitis C infection in Malay Male drug abusers. The selection of the subjects provides novel knowledge in understanding the high occurrence of chronic HCV among drug abusers, a vulnerable and often neglected group of patients. Interleukin-10 (IL-10) rs1800896 and rs1800871, interleukin 6 (IL-6) rs1800795, tumour necrosis factor (TNF)-α rs1800629 and tumour growth factor (TGF)-β1 rs1800471 have been selected for the investigations representing anti and proinflammatory cytokines. A total of 162 subjects were enrolled from various health clinics in Kelantan, Malaysia, and divided into two groups: 76 patients with chronic HCV infection (HP) and 86 control group (HS). The gene polymorphisms were detected through multiplex polymerase chain reaction (PCR), gene expressions by real-time reverse transcriptase polymerase chain reaction (RT-PCR), and the serum cytokine levels were measured by immunoassay. There were significant differences in the frequencies of genotype for IL-10 rs1800896 (p = 0.0422), IL-10 rs1800871 (p = 0.0498), and at the allelic level for IL-10 rs1800896 A versus G allele (p = 0.0142), TGF-β1 rs1800471 (p = 0.0051) and at the allelic level for TGF-β1 rs1800471 G versus C allele (p = 0.0082) in the HP group and the control group. The study discovered a significant difference in gene expression for TNF-α (p = 0.0328) and in the mean serum levels of IL-6, and TGF-β1 in the HP group compared to the HS group (p = 0.0180 and p = 0.0005, respectively). These findings suggest significant associations between gene polymorphisms for IL-10 rs1800896, IL-10 rs1800871, TGF-β1 rs1800471 and susceptibility to HCV infection among Malay male patients with chronic HCV infection. Gene expression of TNF-α and serum expression of IL-10, IL- 6 and TGF-β1 shows a significant association with chronic HCV infection. This study provides a novel insight into the role of cytokines and genetic variation on susceptibility to chronic HCV infection among Malay male drug abusers, discovering potential genetic and serum biomarkers for the disease, and eventually towards precision medicine for chronic HCV infection, particularly for drug abusers.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Noh, Che Ismail Che
author_facet	Noh, Che Ismail Che
author_sort	Noh, Che Ismail Che
title	Study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in Malay male drug abusers
title_short	Study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in Malay male drug abusers
title_full	Study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in Malay male drug abusers
title_fullStr	Study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in Malay male drug abusers
title_full_unstemmed	Study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in Malay male drug abusers
title_sort	study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in malay male drug abusers
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Kesihatan
publishDate	2023
url	http://eprints.usm.my/59784/1/CHE%20ISMAIL%20BIN%20CHE%20NOH%20-%20FINAL%20THESIS%20P-UD001318%28R%29-E.pdf
_version_	1794024054825418752

Study on the serum and gene expression profile of cytokines and the role of cytokine gene polymorphism on susceptibility to hepatitis c infection in Malay male drug abusers

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