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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

Frequency of each tumor necrosis factor α -308 genotype in early and late hepatitis C virus fibrosis patients. Genotyping of TNFα -G308A was conducted in 120 chronic HCV patients (F0-F4) using PCR-RFLP analysis. The frequency of each genotype (GG, GA, AA) was calculated as percentage and compared in early (F0-F2, n = 60) and late (F2-F4, n = 60) HCV fibrosis patients. TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus; RFLP: Restriction fragment length polymorphism.
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Figure 3: Frequency of each tumor necrosis factor α -308 genotype in early and late hepatitis C virus fibrosis patients. Genotyping of TNFα -G308A was conducted in 120 chronic HCV patients (F0-F4) using PCR-RFLP analysis. The frequency of each genotype (GG, GA, AA) was calculated as percentage and compared in early (F0-F2, n = 60) and late (F2-F4, n = 60) HCV fibrosis patients. TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus; RFLP: Restriction fragment length polymorphism.

Mentions: The 120 chronic HCV patients with different fibrosis grade were classified into 60 patients with early fibrosis grade (F0-F1) and 60 patients with late fibrosis grade (F2-F4). Analysis of the frequency of each TNFα genotype showed that early fibrosis patients have 26.7% of AA, 43.9% of AG and 64.6% of GG genotype, which indicates an increasing trend of having the G allele. The AA genotype was detected in 73.3% of late fibrosis patients vs 26.7% of early fibrosis patients (P = 0.05), as shown in Figure 3. In general, the late fibrosis patients had a statistically significant higher rate of A allele than the early fibrosis patients (62.1% vs 37.9% respectively, P = 0.04).


Tumor necrosis factor- α -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients
Frequency of each tumor necrosis factor α -308 genotype in early and late hepatitis C virus fibrosis patients. Genotyping of TNFα -G308A was conducted in 120 chronic HCV patients (F0-F4) using PCR-RFLP analysis. The frequency of each genotype (GG, GA, AA) was calculated as percentage and compared in early (F0-F2, n = 60) and late (F2-F4, n = 60) HCV fibrosis patients. TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus; RFLP: Restriction fragment length polymorphism.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Frequency of each tumor necrosis factor α -308 genotype in early and late hepatitis C virus fibrosis patients. Genotyping of TNFα -G308A was conducted in 120 chronic HCV patients (F0-F4) using PCR-RFLP analysis. The frequency of each genotype (GG, GA, AA) was calculated as percentage and compared in early (F0-F2, n = 60) and late (F2-F4, n = 60) HCV fibrosis patients. TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus; RFLP: Restriction fragment length polymorphism.
Mentions: The 120 chronic HCV patients with different fibrosis grade were classified into 60 patients with early fibrosis grade (F0-F1) and 60 patients with late fibrosis grade (F2-F4). Analysis of the frequency of each TNFα genotype showed that early fibrosis patients have 26.7% of AA, 43.9% of AG and 64.6% of GG genotype, which indicates an increasing trend of having the G allele. The AA genotype was detected in 73.3% of late fibrosis patients vs 26.7% of early fibrosis patients (P = 0.05), as shown in Figure 3. In general, the late fibrosis patients had a statistically significant higher rate of A allele than the early fibrosis patients (62.1% vs 37.9% respectively, P = 0.04).

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