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
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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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