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New Research Establishes Genetic Associations In
Hepatitis C
April 9, 2003 (San Diego, CA) --
Hepatitis C Virus (HCV), as a major agent of non-A, non-B hepatitis
(NANBH), has been described as an insidious disease and a silent
epidemic, mainly because the infection is often sub-clinical. Acute
infection is recognized in a minority of patients and in most cases
the virus results in chronic infections taking 10-20 years before
the emergence of liver disease. In the US, almost four million
individuals are infected and up to 170 million worldwide.
Background
An imbalance in helper T-cell type-1 (Th1) and
type-2 (Th2) cytokines has been suggested as playing an important
role in the cause of chronic viral infections, but this issue is not
resolved in patients with hepatitis C virus (HCV) infection.
Inflammation of the portal and portal areas is a common feature of
chronic hepatitis C. Antigen presenting dendritic, or “tree-like,”
cells are located in the portal area, and infiltrating T-cells are
initially exposed to infected hepatocytes in the peripheral area.
Thus, these areas could be sites of the initial processes of the
immune response in chronic hepatitis C.
The pathogenesis of hepatitis C virus
associated liver injury involves many genes from multiple pathogenic
pathways. Blockade of CC-chemokine receptor 5 (CCR5) has been
proposed as therapy for HIV-1. Therefore, an examination was
conducted to determine if the CCR5-delta32 homozygous genotype has
phenotypic expression other than those related to HIV-1. Other genes
associated with viral infection (RANTES, CD4), and in inflammation
(Interleukin1B) were also reviewed for their possible association.
Hepatitis C virus (HCV) is commonly seen in the
Coachella Valley of Southern California. Genetic Research institute
of the Desert (GRID), a nonprofit research center was established in
the Coachella valley with a goal to investigate genetic aspects of
cancer, as well as infectious and some neurological diseases. This
research effort focused on the genetic variants in the HCV group of
patients compared to normal healthy individuals. Genetic association
could determine the drug responsiveness and aid in treatment;
accordingly, a research objective was to determine genetic variants
associated with the disease and to find the multiple allelic
associations of these genes. The associated genes can be used as
prognostic markers, as well as help design drug for hepatitis.
A New Study
The authors of “Multiple Gene Associations In
Hepatitis ‘C’ Infection, ” are Radhika Gade-Andavolu, PhD from
Genetic Research Institute of the Desert, Rancho Mirage, Gary
Annunziata, DO, and Lawrence A. Cone, MD, DSc, are from the
Eisenhower Medical Center, Rancho Mirage, CA. Their findings are
being presented at Experimental Biology 2003, a meeting
sponsored by the American Physiological Society, being held April
11-15, 2003, at the San Diego Convention Center, San Diego, CA.
Methodology
Patients seeking treatment at Infectious
Diseases and Gastroenterology clinics
at the Eisenhower Medical center participated
in this research. After informed consent was obtained blood was
drawn from patients; DNA was isolated from the blood and used for
analysis. Genomic DNA from 26 hepatitis C patients and 318 healthy
controls was subjected for PCR analysis to determine the genotypes
of four genes.
Results
In this study, the frequency of the SNP’s of
IL1B and RANTES, a 32bp deletion in CCR5 and CD4 pentanucleotide
repeat polymorphisms was evaluated. The findings were reviewed for
association of various genotypes with respect to disease onset and
severity scores, and a statistical analysis was done.
Out of the four genes studied in patients, only
CD4 repeat (p= 0.006) was highly significant with respect to
controls. With the onset of disease relative to age, CD4 (p=
0.02) and IL-B (p= 0.012) were significant, while CCR5 delta
32mutation showed significance with severity score (p=0.08). IL-1B
and RANTES genes showed positive correlation (p= 0.04) with pair
wise bivariate analysis.
Conclusions
These preliminary findings with CD4 indicate a
correlation between dominant Th1 response and disease activity and
progression suggesting a possible role of intrahepatic CD4 T cells
in hepatic injury of HCV infection. In addition the findings of
CCR5, IL1B and its significant correlation with RANTES suggests
their possible roles in the immune response to HCV infection in and
around the portal area by attracting naïve and active T-cells. This
research will continue with the addition of more genes and the
target set numbers of genes are to be pooled to ascertain the risk.
-end-
The American Physiological Society
(APS) is one of the world’s most prestigious organizations for
physiological scientists. These researchers specialize in
understanding the processes and functions underlying human health
and disease. Founded in 1887 the Bethesda, MD-based Society has
more than 10,000 members and publishes 3,800 articles in its 14
peer-reviewed journals each year.
***
Editor’s Note: For receive a copy of the abstract, or to schedule an
interview with a member of the research team, please contact Donna
Krupa at 703.967.2751 (cell), 703.527.7357 (office) or at
djkrupa1@aol.com. Or contact the
APS newsroom at 619.525.6340 between 7:00 AM and 4:00 PM PST April
11-14, 2003.
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