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العنوان
The Potential Association of Apolipoprotein
E and Interleukin-28B Genetic Variants
with Hepatitis C Virus Recurrence
Following Liver Transplantation /
المؤلف
Mohamed,Aya Mohamed Abd Elsamee.
هيئة الاعداد
باحث / أية محمد عبد السميع محمد
مشرف / شاديــة عبد الحميــد فتحــى
مشرف / ســارة حســـن أبو عجــــوة
مشرف / محمــد أحمـد محمـد علـى
تاريخ النشر
2020
عدد الصفحات
212p.;
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الكيمياء الحيوية ، علم الوراثة والبيولوجيا الجزيئية
تاريخ الإجازة
1/1/2020
مكان الإجازة
جامعة عين شمس - كلية العلوم - الكيمياء الحيوية
الفهرس
Only 14 pages are availabe for public view

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Abstract

Liver disease caused by the hepatitis C virus (HCV) is
the main indication for liver transplantation in Western
countries. The highest prevalence of hepatitis c infection is
in Egypt over the world, averaging 15-25% in rural
communities, with >90% having HCV genotype 4.
Furthermore, reports indicate that HCV genotype 4 is
starting to unfold from its native African and geographical
region origins to countries of Southern Europe and in some
foci in the USA. Egyptian population has a heavy burden of
liver disease, mostly due to chronic infection with HCV.
An increasing cause of mortality in Egypt in the last decade
is End stage liver disease (ESLD) secondary to HCV
infection. HCV recurrence represents a universal
phenomenon after liver transplantation and HCV RNA
concentration increases progressively as early as 12h after
graft reperfusion. The spontaneous clearance of HCV
infection after transplant is very rare. It has been reported
that the main indication for liver transplantation is HCVrelated
ESLD and represents 89.8% of cases in Egypt.
Because of the impact of HCV recurrence on graft and
patient survival, many treatment ways are updated. Early with living donor liver transplantation (LDLT)
in the setting of chronic HCV infection suggested a less
successful outcome than from deceased donors. Liver
transplantation (LT) provides a novel chance to analyze the
contribution of the liver to the synthesis and degradation of
genetically polymorphic plasma proteins. In humans, 3
major co-dominant alleles (E2, E3, E4) for a single gene
locus coded ApoE. A change that causes profound
functional consequences at both the cellular and molecular
levels. Genome-wide association studies have shown that
SNPs in or near the interleukin-28B (IL-28B) gene are
significantly associated with the treatment outcome for
HCV-infected patients.
The aim of the present study is to evaluate the
potential association of Apolipoprotein E and Interleukin-
28B single nucleotide polymorphisms (SNPs) in donors
and/or recipients with HCV recurrence following liver
transplantation.
Three SNPs were genotyped (two loci [rs12979860
and rs8099917]) in IL-28 and one in apolipoprotein E3 in
100 DNA samples collected from HCV-infected patients
using TaqMan Allelic Discrimination assay and PCRRFLP,
respectively. HCV-RNA levels were determined before transplantation and 24 months later by quantitative
real-time polymerase chain reaction (qPCR).
Recipients who had the favorable IL-28 rs12979860
homozygous allele (CC) had a higher rate of SVR than
those with the heterozygous allele. Recipients who had the
favorable IL-28 rs8099917 homozygous allele (TT) had a
higher rate of SVR than those with the heterozygous allele.
Regarding ApoE, different ApoE genotypes between
donors and recipients were associated with a higher rate of
SVR than those with the same genotype.
In conclusion, to improve prediction of HCV
recurrence, different clinical and genomic data have been
combined in logistic models. The simultaneous
determination of two IL28B SNPs could be useful in some
HCV infected patients to guide therapeutic decisions and
improve treatment management and should therefore be
included in the panel of pre-treatment evaluations.
Furthermore, we hope that ApoE genotyping may be a
helpful element to support clinical decision-making in these
patients. If these results were confirmed in a wider series,
ApoE genotyping might prove to be a precious point to take
into consideration during antiviral treatment of recurrent
HCV infection.