Polymorphisms of hemochromatosis, and alpha-1 antitrypsin genes in Egyptian HCV patients with and without hepatocellular carcinoma

Gharib, Amal F.; Karam, Rehab A.; Pasha, Heba F.; Radwan, Mohamed; Elsawy, Wael H.

doi:10.1016/j.gene.2011.08.010

Cited by 20 publications

(21 citation statements)

References 35 publications

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“…In addition, the higher serum iron levels seen in our patients with HCV infection may have been caused by various factors other than HFE gene mutations; e.g., hepatocyte necrosis or increased intestinal iron uptake [28] . In contrast to previous reports [10,11] , we did not detect an association between HCV infection and alpha-1 antitrypsin deficiency. Again, this may have been due to the small number of patients in our study and/or the fact that liver symptoms in patients with alpha-1 antitrypsin deficiency more commonly manifest in childhood or late adulthood.…”

Section: Discussioncontrasting

confidence: 99%

“…Most reports on the coexistence of monogenic liver diseases and HCV infection have focused primarily on hereditary hemochromatosis [7] because elevated iron levels are necessary for viral replication [8,9] . Although the associations of HCV infection with alpha-1 antitrypsin deficiency [10,11] and Gilbert's syndrome [12][13][14] have been investigated, the association of HCV infection with Wilson's disease remains unclear. Copper reportedly plays a potential role in the development of HCV infection [15,16] .…”

Section: Introductionmentioning

confidence: 99%

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Association between inherited monogenic liver disorders and chronic hepatitis C

Piekuse¹,

Kreile²,

Zariņa³

et al. 2014

WJH

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AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C (55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene (mutation): ATP7B (H1069Q), HFE (C282Y, H63D), UGT1A1 (TA)7, and SERPINA1 (PiZ)] were detected by polymerase chain reaction (PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS:The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61 (76%), 7 (9%), and 12 (15%) patients, respectively. Among all 86 patients, 50 (58%) reached an early viral response and 70 (81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Casecontrol analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls (patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The (TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels (beta regression coefficient = -295.7, P = 0.0087). CONCLUSION:Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association between inherited monogenic liver disorders and chronic hepatitis C

Piekuse¹,

Kreile²,

Zariņa³

et al. 2014

WJH

View full text Add to dashboard Cite

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“…[34] who found that the S allele and both MS and SS genotypes of A1AT were significantly higher in the Egyptian patients with HCV liver cirrhosis than in controls. On the other hand, there was no significant difference between the alleles or genotypes of S or Z mutations of A1AT in the Egyptian patients with hepatocellular carcinoma compared to controls [35]. …”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection

Motawi

Shaker

Hussein

et al. 2016

Balkan Journal of Medical Genetics

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Hepatitis C virus (HCV) infection represents a serious health problem. The –174 G/C mutation in the pro inflammatory cytokine interleukin-6 (IL-6) is associated with developing liver diseases. Likewise, the S and Z mutations in the serine protease inhibitor α1-antitrypsin (A1AT) are associated with pulmonary emphysema and/or liver cirrhosis. We explored the distribution of the single nucleotide polymorphisms (SNPs) of IL-6 and A1AT genes in chronic HCV-infected patients and evaluated their impact on the progression of liver cirrhosis.One hundred and fifty Egyptian HCV-infected patients together with 100 healthy controls were enrolled in this study. The patient groups were subdivided into chronic hepatitis patients (n = 85) and cirrhotic patients (n = 65). The SNP of IL-6 (–174 G/C, rs1800795), A1AT Z mutation (342 Glu/Lys, rs28929474) and A1AT S mutation (264 Glu/Val, rs17580) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Cirrhotic patients exhibited significantly increased frequency of the A1AT S allele compared with the controls (34.6 vs. 5.0%), while the chronic hepatitis patients showed a higher frequency of the A1AT Z allele compared with the controls (14.7 vs. 2.5%). Remarkably, IL-6 (CC genotype) was detected only in the chronic hepatitis patients. Multivariate regression analysis showed that aspartate transaminase (AST) and the S alleles of A1AT, represented as SS+MS genotypes, were significantly independent predictors for development of liver cirrhosis. We concluded that inheritance of deficient S and Z alleles of the A1AT gene but not IL-6 (–174 G/C), were associated with progressive liver diseases.

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“…The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method was performed to genotype the HCV patients and the healthy controls, based on the study of Gharib et al (17). The PCR process was performed for each location using a primer pair, as listed in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Haplotype Analysis of Hemochromatosis Gene Polymorphisms in Chronic Hepatitis C Virus Infection: A Case Control Study

Gerayli¹,

Pasdar²,

Shakeri³

et al. 2016

Iran Red Crescent Med J

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BackgroundChronic hepatitis C virus (HCV) infection is frequently associated with elevated serum iron markers. Polymorphisms in the hemochromatosis (HFE) genes are responsible for iron accumulation in most cases of hemochromatosis, and may play a role in HCV infection.ObjectivesWe aimed to assess the prevalence of HFE gene polymorphisms in a group of Iranian HCV-infected patients, and to explore the association of these polymorphisms with HCV infection.Patients and MethodsHFE gene polymorphisms were examined in a total of 69 HCV patients and 69 healthy controls using polymerase chain reaction and restriction fragment length polymorphism techniques. Haplotype and diplotype analyses were performed using PHASE software.ResultsIn a recessive analysis model of the His63Asp (H63D) locus (HH vs. HD + DD), the HH genotype was more common in patients compared to controls (adjusted P = 0.012; OR = 6.42 [95% CI: 1.51 - 27.33]). Also, in a recessive analysis model of the Cys282Tyr (C282Y) locus (CC vs. CY + YY), the CC genotype was more frequent in patients compared to controls (adjusted P = 0.03; OR = 5.06 [95% CI: 1.13 - 22.06]). In addition, there was a significant association between the HC haplotype and the HCDC diplotype and HCV infection.ConclusionsPolymorphism in the hemochromatosis gene may confer some degree of risk for HCV infection, and individuals carrying the H and C alleles may be susceptible to this disease; however, a larger sample of HCV patients and healthy individuals may be necessary to further illustrate the role of these polymorphisms in HCV.

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Polymorphisms of hemochromatosis, and alpha-1 antitrypsin genes in Egyptian HCV patients with and without hepatocellular carcinoma

Cited by 20 publications

References 35 publications

Association between inherited monogenic liver disorders and chronic hepatitis C

Association between inherited monogenic liver disorders and chronic hepatitis C

Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection

Haplotype Analysis of Hemochromatosis Gene Polymorphisms in Chronic Hepatitis C Virus Infection: A Case Control Study

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