Impact of genetic SLC28 transporter and ITPA variants on ribavirin 21 serum level, hemoglobin drop and therapeutic response in patients with HCV infection
Details
Serval ID
serval:BIB_0082CCE30206
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Impact of genetic SLC28 transporter and ITPA variants on ribavirin 21 serum level, hemoglobin drop and therapeutic response in patients with HCV infection
Title of the conference
Annual Meeting of the Swiss Society of Gastroenterology, Swiss Society of Visceral Surgery, Swiss Association of the Study of the Liver and Swiss Society of Clinical Nutrition
Address
Interlaken, Switzerland, September 20-21, 2012
ISBN
1424-7860
ISSN-L
0036-7672
Publication state
Published
Issued date
2012
Volume
142
Series
Swiss Medical Weekly
Pages
S7
Language
english
Abstract
Background: T reatment o f chronic hepatitis C i s evolving, a nd direct
acting antivirals ( DAAs) are now a dded to p egylated interferon-α ( Peg-
INF-α) and ribavirin (RBV) for the treatment o f hepatitis C v irus ( HCV)
genotype 1 infection. DAAs c ause d ifferent side effects and can even
worsen RBV induced hemolytic anemia. T herefore, identifying host
genetic d eterminants of R BV bioavailability and therapeutic e fficacy will
remain crucial for individualized treatment. Recent d ata showed
associations between R BV induced h emolytic anemia and genetic
polymorphisms o f concentrative nucleoside transporters s uch as C NT3
(SLC28A3) and i nosine t riphosphatase (ITPA). T o analyze t he
association of genetic variants of SLC28 transporters and ITPA with RBV
induced hemolytic anemia and treatment o utcome. Methods: I n our
study, 173 patients f rom t he S wiss Hepatitis C C ohort Study and 2 2
patients from Swiss Association for the Study of the Liver study 24 (61%
HCV g enotype 1, 3 9% genotypes 2 o r 3) were analyzed for SLC28A2
single nucleotide p olymorphism (SNP) rs11854484, SLC28A3
rs56350726 and SLC28A3 rs10868138 as well as ITPA SNPs rs1127354
and rs7270101. RBV serum levels during treatment were measured in 49
patients. Results: SLC28A2 r s11854484 genotype TT was associated
with significantly higher dosage- and body weight-adjusted RBV levels as
compared to genotypes TC and CC (p=0.04 and p=0.02 at weeks 4 and
8, respectively). ITPA SNPs rs1127354 and rs7270101 were associated
with h emolytic a nemia both in genotype as w ell as i n allelic a nalyses.
SLC28A3 rs56350726 genotype TT (vs. AT/AA, RR=2.1; 95% CI 1.1-4.1)
as well as the T allele (vs. A; RR=1.8, 95% CI 1.1-3.2) were associated
with increased SVR rates. The combined analysis of overall ITPA activity
and SLC28 v ariants together revealed n o significant a dditive effects on
either treatment-related anemia or SVR. Conclusions: T he newly
identified association between RBV serum levels a nd SLC28A2
rs11854484 genotype as well as the replicated association of ITPA and
SLC28A3 g enetic p olymorphisms w ith RBV induced hemolytic anemia
and treatment r esponse underpin the need for further studies on host
genetic d eterminants of R BV bioavailability and therapeutic e fficacy f or
individualized treatment of chronic hepatitis C.
acting antivirals ( DAAs) are now a dded to p egylated interferon-α ( Peg-
INF-α) and ribavirin (RBV) for the treatment o f hepatitis C v irus ( HCV)
genotype 1 infection. DAAs c ause d ifferent side effects and can even
worsen RBV induced hemolytic anemia. T herefore, identifying host
genetic d eterminants of R BV bioavailability and therapeutic e fficacy will
remain crucial for individualized treatment. Recent d ata showed
associations between R BV induced h emolytic anemia and genetic
polymorphisms o f concentrative nucleoside transporters s uch as C NT3
(SLC28A3) and i nosine t riphosphatase (ITPA). T o analyze t he
association of genetic variants of SLC28 transporters and ITPA with RBV
induced hemolytic anemia and treatment o utcome. Methods: I n our
study, 173 patients f rom t he S wiss Hepatitis C C ohort Study and 2 2
patients from Swiss Association for the Study of the Liver study 24 (61%
HCV g enotype 1, 3 9% genotypes 2 o r 3) were analyzed for SLC28A2
single nucleotide p olymorphism (SNP) rs11854484, SLC28A3
rs56350726 and SLC28A3 rs10868138 as well as ITPA SNPs rs1127354
and rs7270101. RBV serum levels during treatment were measured in 49
patients. Results: SLC28A2 r s11854484 genotype TT was associated
with significantly higher dosage- and body weight-adjusted RBV levels as
compared to genotypes TC and CC (p=0.04 and p=0.02 at weeks 4 and
8, respectively). ITPA SNPs rs1127354 and rs7270101 were associated
with h emolytic a nemia both in genotype as w ell as i n allelic a nalyses.
SLC28A3 rs56350726 genotype TT (vs. AT/AA, RR=2.1; 95% CI 1.1-4.1)
as well as the T allele (vs. A; RR=1.8, 95% CI 1.1-3.2) were associated
with increased SVR rates. The combined analysis of overall ITPA activity
and SLC28 v ariants together revealed n o significant a dditive effects on
either treatment-related anemia or SVR. Conclusions: T he newly
identified association between RBV serum levels a nd SLC28A2
rs11854484 genotype as well as the replicated association of ITPA and
SLC28A3 g enetic p olymorphisms w ith RBV induced hemolytic anemia
and treatment r esponse underpin the need for further studies on host
genetic d eterminants of R BV bioavailability and therapeutic e fficacy f or
individualized treatment of chronic hepatitis C.
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