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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

Distribution of tumor necrosis factor α -G308A polymorphism in hepatitis C virus infected patients with different fibrosis grade (F0-F4). Genotyping of TNFα -G308A was conducted for 120 chronic HCV patients (F0-F4) using PCR-RFLP analysis. The different TNFα -G308A genotypes were represented as percentages and compared among HCV patients with different fibrosis grades: F0 (n = 30), F1 (n = 30), F2-F3 (n = 30), F4 (n = 30). TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus; RFLP: Restriction fragment length polymorphism.
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Figure 2: Distribution of tumor necrosis factor α -G308A polymorphism in hepatitis C virus infected patients with different fibrosis grade (F0-F4). Genotyping of TNFα -G308A was conducted for 120 chronic HCV patients (F0-F4) using PCR-RFLP analysis. The different TNFα -G308A genotypes were represented as percentages and compared among HCV patients with different fibrosis grades: F0 (n = 30), F1 (n = 30), F2-F3 (n = 30), F4 (n = 30). TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus; RFLP: Restriction fragment length polymorphism.

Mentions: Distribution of TNFα -G308A genotypes in HCV infected patients and controls are shown in Table 2. The results showed that the TNFα -G308A SNP frequency was significantly different between controls and HCV infected patients (P = 0.001). The TNFα -G308A genotypes in the controls were 66.6% GG, 30% GA and 3.3% AA. The GG genotype in controls (66.6%) is higher than in chronic HCV patients (40%), while the chronic HCV patients had higher GA and AA genotypes (47.5% and 12.5%) compared to controls (30% and 3.3%). Moreover, the G allele is more frequent than the A allele in both controls (81.7% vs 18.3%) and HCV-infected patients (63.8% vs 36.3%), with statistically significant difference (P = 0.002). The distribution of TNFα genotypes in HCV patients with different fibrosis grade is shown in Figure 2. The TNFα GG genotype was 60% in F0, 43.3% in F1, 33.3% in F2-F3, and 23.3% in F4 patients, while the (GA + AA) genotypes were 40% in F0, 56.7% in F1, 66.6% in F2-F3, and 76.6% in F4 patients.


Tumor necrosis factor- α -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients
Distribution of tumor necrosis factor α -G308A polymorphism in hepatitis C virus infected patients with different fibrosis grade (F0-F4). Genotyping of TNFα -G308A was conducted for 120 chronic HCV patients (F0-F4) using PCR-RFLP analysis. The different TNFα -G308A genotypes were represented as percentages and compared among HCV patients with different fibrosis grades: F0 (n = 30), F1 (n = 30), F2-F3 (n = 30), F4 (n = 30). 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 2: Distribution of tumor necrosis factor α -G308A polymorphism in hepatitis C virus infected patients with different fibrosis grade (F0-F4). Genotyping of TNFα -G308A was conducted for 120 chronic HCV patients (F0-F4) using PCR-RFLP analysis. The different TNFα -G308A genotypes were represented as percentages and compared among HCV patients with different fibrosis grades: F0 (n = 30), F1 (n = 30), F2-F3 (n = 30), F4 (n = 30). TNFα: Tumor necrosis factor alpha; HCV: Hepatitis C virus; RFLP: Restriction fragment length polymorphism.
Mentions: Distribution of TNFα -G308A genotypes in HCV infected patients and controls are shown in Table 2. The results showed that the TNFα -G308A SNP frequency was significantly different between controls and HCV infected patients (P = 0.001). The TNFα -G308A genotypes in the controls were 66.6% GG, 30% GA and 3.3% AA. The GG genotype in controls (66.6%) is higher than in chronic HCV patients (40%), while the chronic HCV patients had higher GA and AA genotypes (47.5% and 12.5%) compared to controls (30% and 3.3%). Moreover, the G allele is more frequent than the A allele in both controls (81.7% vs 18.3%) and HCV-infected patients (63.8% vs 36.3%), with statistically significant difference (P = 0.002). The distribution of TNFα genotypes in HCV patients with different fibrosis grade is shown in Figure 2. The TNFα GG genotype was 60% in F0, 43.3% in F1, 33.3% in F2-F3, and 23.3% in F4 patients, while the (GA + AA) genotypes were 40% in F0, 56.7% in F1, 66.6% in F2-F3, and 76.6% in 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