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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| Format: | Thesis |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| 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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| Summary: | 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. |
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