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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RESULTS
The Demographic and Biochemical Parameters
of the Studied Groups. In this study, we recruited two
groups of chronic HCV-infected patients; the chronic hepatic
patients and the cirrhotic patients in addition to the
control group. We found that the chronic hepatic patients
exhibited significantly higher values of ALT, AST and
ALP compared with the control group (p <0.05). In the same way, the cirrhotic patient group exhibited significantly
higher activities of ALT, AST and ALP in addition
to higher values of total bilirubin, prothrombin time and
AFP and lower albumin compared to the control group (p
<0.05). Interestingly, the cirrhotic patient group exhibited
significantly higher values of AST, albumin, prothrombin
time, AFP and fibrosis score compared to the chronic hepatic
patient group (p <0.05). These results confirm the
progression of the end stage complications associated with
HCV infection in the cirrhotic patients. The demographic
and biochemical parameters of all studied groups are summarized
in Table 1.
Frequency of Interleukin 6 Genotypes and Alleles
of the Studied Groups. The SNP of IL-6 (–174 G/C, rs
1800795) was detected in the control, chronic hepatic and
cirrhotic patients by the PCR-RFLP method. We found
that the G allele was distributed at 100.0% in the control
group, while the C allele was found only in the chronic
hepatitis and cirrhotic patients at frequencies of 17.6 and
19.2%, respectively (Table 2). In more detail, the IL-6
(GG genotype) showed significantly lower frequency in
the cirrhotic patients (61.5%) when compared to the control
group (100.0%) at p <0.05. On the other hand, the
IL-6 (CC genotype) was only found in the chronic hepatic
patients (5.9% frequency), while the heterozygous IL-6
(GC genotype) was detected in both chronic hepatic and
cirrhotic patients at 23.5 and 38.5% frequencies, respectively
(Table 2).
Frequency of α1-Antitrypsin Genotypes and Alleles
of the Studied Groups. The S (264 Glu/Val, rs17580)
and Z (342 Glu/Lys, rs28929474) mutations of the A1AT
gene were detected in the control, chronic hepatic and cirrhotic
patients by the PCR-RFLP method. We found that
the wild type M allele was the most common allele in all groups. However, the frequency of the M allele decreased
significantly in cirrhotic patients (65.4%) when compared
to the control group (92.5%). Interestingly, the cirrhotic
patients also showed a significantly increased frequency of
the S allele (34.6%) compared to the control group (5.0%),
while the Z allele was not detected in the cirrhotic patients
(Table 3). The distribution of the A1AT genotypes revealed
that the A1AT (SS genotype) was only detected in the
cirrhotic patients (23.1% frequency) compared to control
and chronic hepatic patients (both at 0.0% frequencies). In
the same way, the A1AT (ZZ genotype) was only detected
in the chronic hepatic patients (11.8% frequency) when
compared to control and cirrhotic patients. The heterozygous
MS and MZ genotypes were detected mostly in the
chronic HCV patients (Table 3).
The Biochemical Parameters Associated with Different
Interleukin 6 Genotypes. As the low producer,
IL-6 (CC genotype), was detected only in the chronic hepatitis
patients, comparing the CC genotype with the high
producer IL-6 (GG+GC) genotypes in the same group did
not show significant increased values of ALT, AST, ALP,
total and direct bilirubin or AFP (Table 4). These findings
indicate that inheritance of the IL-6 (CC genotype) is not
associated with increased risk of developing progressive
liver diseases.
The Biochemical Parameters Associated with Different
α1-Antitrypsin Genotypes. The chronic hepatitis
patients with the Z allele (MZ+ZZ genotypes) showed a
significantly increased AST activity when compared to
the chronic hepatitis patients with either the MM or MS
genotypes (p <0.05). Interestingly, the cirrhotic patients
with the S allele (MS+SS genotypes) showed significantly
increased levels of AST, ALT, total bilirubin, direct bilirubin
and lower albumin levels when compared with the cirrhotic liver patients with the A1AT (MM genotype) at p
<0.05 (Table 5). These results indicate that inheritance of
A1AT (S or Z allele) increases the severity of liver disease
in either cirrhotic or chronic hepatitis patients, respectively.
Multivariate regression analyses showed that AST (p
= 0.003, OR = 1.6, 95% CI = 1.3-2.0) and the S allele of
A1AT represented as SS+MS genotypes (p = 0.001, OR
= 7.7, 95% CI = 3.4-17.4) to be significantly independent
predictors for development of liver cirrhosis. Although
the IL-6 gene is known to regulate the expression of acute
phase reactants such as A1AT, we did not find a statistically
significant correlation between any of the genotypes
of IL-6 (GG, GC, CC) and any of the A1AT (MM, MS,
MZ, SS, ZZ) genotypes.
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