POLYMORPHISMS OF α1-ANTITRYPSIN AND INTERLEUKIN-6 GENES AND THE PROGRESSION OF HEPATIC CIRRHOSIS IN PATIENTS WITH A HEPATITIS C VIRUS INFECTION
Motawi T, Shaker OG, Hussein RM, Houssen M
*Corresponding Author: Rasha M. Hussein, Ph.D., Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Salah Salem Street, 62511, Beni-Suef, Egypt. Tel: +20-12-0013-6515. Fax: +20-82-2317-958. E-mail: rasha.hussein@ pharm.bsu.edu.eg
page: 35

DISCUSSION

In the present study, we investigated the association between IL-6 and A1AT SNPs and the progression of liver cirrhosis in Egyptian HCV-infected patients. In Egypt, numerous risk factors such as age, poverty, blood transfusion and intravenous anti-schistosomal treatment are associated with increased risk of being infected with HCV. Altogether, they render the numbers of HCV-infected patients to reach epidemic proportions [23,24]. Our analysis of the SNP IL-6 (174 G/C) revealed that the G allele represents about 87.7% frequency in all subjects (controls and patients), while the C allele represents only a 12.3% frequency. These results are compatible with the findings that the G allele is highly distributed in non Caucasian populations compared with Caucasian population [25]. Interestingly, the CC genotype is only found in the chronic hepatitis patients but not in the control group or the cirrhotic patients. However, this CC genotype was not associated with significantly increased liver parameters in the chronic hepatitis patient group. The absence of the C allele from the control group may be attributed to the small size of our analyzed sample. However, our findings are still compatible with the few studies that examined the correlation between IL-6 polymorphisms and the progression of liver fibrosis in HCV-infected patients. For instance, Barrett et al. [26] found a positive correlation between IL-6 (174 C/C) genotype and HCV clearance in an Irish population sample. On the other hand, Pereira et al. [27] found no difference in the frequency of IL-6 alleles at the 174 locus between controls and HCV-infected patients in the South American population. This can be explained because chronic hepatitis patients with low IL-6 producer genotypes (CC) are less susceptible to development of progressive liver diseases after HCV infection. Moreover, the chronic exposure of hepatocytes to IL-6, probably produced by the high producer genotypes (GG and GC), results in increased induction of the proapoptotic proteins: Bax, caspase 9 and cytochrome C that eventually lead to liver cell death [28]. To date, our study is the first one to describe the distribution of the IL-6 (-174 G/C) genotypes in Egyptian chronic hepatitis patients. For example, the polymorphisms of IL-4, IL-10 and IL-28B cytokines but not IL-6 were previously studied in the Egyptian HCVinfected patients to determine their impact on the response to antiviral treatments [29,30]. However, the frequency of IL-6 (174 CC) genotype was found to be higher in Egyptian patients with other diseases such as intravascular coagulopathy in neonatal sepsis [31] and type 2 DM (T2DM) [32]. It is worth mentioning that Zekri et al. [33] measured the level of IL-6 in the sera of Egyptian patients with hepatocellular carcinoma by the ELISA method and found that they had a lower IL-6 level in comparison to asymptomatic HCV carriers. Regarding A1AT mutations, our results showed that the highest frequency of the S allele (MS+SS genotypes) was found in the cirrhotic patients and it was associated with increased activity of liver enzymes and decreased serum albumin. Interestingly, the highest frequency of Z allele (MZ+ZZ genotypes) was found in the chronic hepatitis patients and was significantly associated with high levels of AST. We cannot exclude the existence of any of the deficient alleles in both groups due to the small number of patients in each group. Nevertheless, our results are compatible with Settin et al. [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]. It is widely accepted that the epidemiology of the A1AT gene deficiency is distributed worldwide and not restricted to Northern Europe as thought before. For example, in a study comprising around 97 countries from different geographic regions worldwide, the prevalence of the S allele in the Egyptian population was estimated at 57.1 cases/1000 population, while the Z allele was estimated at 28.6 cases/1000 population [36]. Our findings indicate that the presence of the Z allele in the chronic hepatitis patients and the S allele in the liver cirrhotic patients are associated with significantly aggressive liver disease.



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