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Tumor necrosis factor- α -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients

View Article: PubMed Central - PubMed

ABSTRACT

Aim: To investigate the association of tumor necrosis factor alpha (TNFα) -G308A polymorphism with different liver pathological changes in treatment-naïve Egyptian patients infected with hepatitis C virus (HCV) genotype 4.

Methods: This study included 180 subjects, composed of 120 treatment-naïve chronic HCV patients with different fibrosis grades (F0-F4) and 60 healthy controls. The TNFα -G308A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis. The TNFα protein was detected by enzyme-linked immunosorbent assay. The influence of different TNFα -G308A genotypes on TNFα expression and liver disease progression were statistically analyzed. The OR and 95%CI were calculated to assess the relative risk confidence.

Results: Current data showed that the TNFα -G308A SNP frequency was significantly different between controls and HCV infected patients (P = 0.001). Both the AA genotype and A allele were significantly higher in late fibrosis patients (F2-F4, n = 60) than in early fibrosis patients (F0-F1, n = 60) (P = 0.05, 0.04 respectively). Moreover, the GA or AA genotypes increased the TNFα serum level greater than the GG genotype (P = 0.002). The results showed a clear association between severe liver pathological conditions (inflammation, steatosis and fibrosis) and (GA + AA) genotypes (P = 0.035, 0.03, 0.04 respectively). The stepwise logistic regression analysis showed that the TNFα genotypes (GA + AA) were significantly associated with liver inflammation (OR = 3.776, 95%CI: 1.399-10.194, P = 0.009), severe steatosis (OR = 4.49, 95%CI: 1.441-14.0, P = 0.010) and fibrosis progression (OR = 2.84, 95%CI: 1.080-7.472, P = 0.034). Also, the A allele was an independent risk factor for liver inflammation (P = 0.003), steatosis (P = 0.003) and fibrosis (P = 0.014).

Conclusion: TNFα SNP at nucleotide -308 represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected patients

No MeSH data available.


Related in: MedlinePlus

Effect of different tumor necrosis factor α genotypes on liver pathological parameters (inflammation, steatosis and fibrosis). The effect of high expressing TNFα genotypes (GA + AA) were statistically compared with the low expressing TNFα genotype (GG), and the results showed strong effect of (GA + AA) genotypes on liver inflammation (P = 0.007), steatosis (P = 0.005) and fibrosis (P = 0.032). P ≤ 0.05 is considered significant while P ≤ 0.01 is highly significant. TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus.
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Figure 5: Effect of different tumor necrosis factor α genotypes on liver pathological parameters (inflammation, steatosis and fibrosis). The effect of high expressing TNFα genotypes (GA + AA) were statistically compared with the low expressing TNFα genotype (GG), and the results showed strong effect of (GA + AA) genotypes on liver inflammation (P = 0.007), steatosis (P = 0.005) and fibrosis (P = 0.032). P ≤ 0.05 is considered significant while P ≤ 0.01 is highly significant. TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus.

Mentions: The influence of different TNFα genotypes on hepatic parameters and liver pathology (liver inflammation, steatosis, and fibrosis) is shown in Table 4. The results demonstrated that TNFα AA genotype patients have significantly higher levels of AST, ALT, ALP and total bilirubin than GG patients (P = 0.0003, 0.0001, 0.002 and 0.0002 respectively). Patients with AA genotype have significantly lower level of albumin and platelets count (P = 0.01 and 0.036 respectively). Moreover, the effect of serum TNFα level expressed by genotypes (GA and AA) on liver inflammation, steatosis and fibrosis are shown in Figure 5. The results showed that genotypes GA or AA which express higher TNF serum level were found in 69.7% of high liver inflammation (A2-A3) patients, in 73.9% of severe steatotic patients, and in 66.7% of late fibrotic (F2-F4) patients.


Tumor necrosis factor- α -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients
Effect of different tumor necrosis factor α genotypes on liver pathological parameters (inflammation, steatosis and fibrosis). The effect of high expressing TNFα genotypes (GA + AA) were statistically compared with the low expressing TNFα genotype (GG), and the results showed strong effect of (GA + AA) genotypes on liver inflammation (P = 0.007), steatosis (P = 0.005) and fibrosis (P = 0.032). P ≤ 0.05 is considered significant while P ≤ 0.01 is highly significant. TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5016377&req=5

Figure 5: Effect of different tumor necrosis factor α genotypes on liver pathological parameters (inflammation, steatosis and fibrosis). The effect of high expressing TNFα genotypes (GA + AA) were statistically compared with the low expressing TNFα genotype (GG), and the results showed strong effect of (GA + AA) genotypes on liver inflammation (P = 0.007), steatosis (P = 0.005) and fibrosis (P = 0.032). P ≤ 0.05 is considered significant while P ≤ 0.01 is highly significant. TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus.
Mentions: The influence of different TNFα genotypes on hepatic parameters and liver pathology (liver inflammation, steatosis, and fibrosis) is shown in Table 4. The results demonstrated that TNFα AA genotype patients have significantly higher levels of AST, ALT, ALP and total bilirubin than GG patients (P = 0.0003, 0.0001, 0.002 and 0.0002 respectively). Patients with AA genotype have significantly lower level of albumin and platelets count (P = 0.01 and 0.036 respectively). Moreover, the effect of serum TNFα level expressed by genotypes (GA and AA) on liver inflammation, steatosis and fibrosis are shown in Figure 5. The results showed that genotypes GA or AA which express higher TNF serum level were found in 69.7% of high liver inflammation (A2-A3) patients, in 73.9% of severe steatotic patients, and in 66.7% of late fibrotic (F2-F4) patients.

View Article: PubMed Central - PubMed

ABSTRACT

Aim: To investigate the association of tumor necrosis factor alpha (TNFα) -G308A polymorphism with different liver pathological changes in treatment-naïve Egyptian patients infected with hepatitis C virus (HCV) genotype 4.

Methods: This study included 180 subjects, composed of 120 treatment-naïve chronic HCV patients with different fibrosis grades (F0-F4) and 60 healthy controls. The TNFα -G308A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis. The TNFα protein was detected by enzyme-linked immunosorbent assay. The influence of different TNFα -G308A genotypes on TNFα expression and liver disease progression were statistically analyzed. The OR and 95%CI were calculated to assess the relative risk confidence.

Results: Current data showed that the TNFα -G308A SNP frequency was significantly different between controls and HCV infected patients (P = 0.001). Both the AA genotype and A allele were significantly higher in late fibrosis patients (F2-F4, n = 60) than in early fibrosis patients (F0-F1, n = 60) (P = 0.05, 0.04 respectively). Moreover, the GA or AA genotypes increased the TNFα serum level greater than the GG genotype (P = 0.002). The results showed a clear association between severe liver pathological conditions (inflammation, steatosis and fibrosis) and (GA + AA) genotypes (P = 0.035, 0.03, 0.04 respectively). The stepwise logistic regression analysis showed that the TNFα genotypes (GA + AA) were significantly associated with liver inflammation (OR = 3.776, 95%CI: 1.399-10.194, P = 0.009), severe steatosis (OR = 4.49, 95%CI: 1.441-14.0, P = 0.010) and fibrosis progression (OR = 2.84, 95%CI: 1.080-7.472, P = 0.034). Also, the A allele was an independent risk factor for liver inflammation (P = 0.003), steatosis (P = 0.003) and fibrosis (P = 0.014).

Conclusion: TNFα SNP at nucleotide -308 represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected patients

No MeSH data available.


Related in: MedlinePlus