Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort.
(2012) In European Journal of Gastroenterology and Hepathology 24(8). p.890-896- Abstract
- OBJECTIVES:
Two functional genetic variants in the inosine triphosphatase (ITPA) gene have been shown to be strongly associated with protection from ribavirin (RBV)-induced hemolysis. We aimed at evaluating this finding in a chronic hepatitis C genotype 2/3 cohort with a predominance of genotype 3 patients where available data are scarce. A second objective was to determine whether a protective association translated into the need for RBV reduction and hence a possible impact on treatment response.
METHODS:
Overall, 457 patients were recruited from two trials of genotype 2/3 patients treated with pegylated interferon α-2b and weight-based RBV. rs1127354 and rs7270101 were genotyped and a composite... (More) - OBJECTIVES:
Two functional genetic variants in the inosine triphosphatase (ITPA) gene have been shown to be strongly associated with protection from ribavirin (RBV)-induced hemolysis. We aimed at evaluating this finding in a chronic hepatitis C genotype 2/3 cohort with a predominance of genotype 3 patients where available data are scarce. A second objective was to determine whether a protective association translated into the need for RBV reduction and hence a possible impact on treatment response.
METHODS:
Overall, 457 patients were recruited from two trials of genotype 2/3 patients treated with pegylated interferon α-2b and weight-based RBV. rs1127354 and rs7270101 were genotyped and a composite ITPAase deficiency variable was graded according to the two single nucleotide polymorphisms. The primary endpoints were hemoglobin (Hb) decline from baseline and Hb decline of more than 3 g/dl at week 4.
RESULTS:
Both single nucleotide polymorphisms and the composite ITPAase deficiency variable were strongly and independently associated with protection from a decline in Hb at week 4 in multivariate linear regression models (Prs1127354=7.0×10, Prs7270101=0.0036, PITPase deficiency variable =6.3×10). Patients with any degree of reduced ITPAase activity were less likely to have their RBV dose reduced (odds ratio 0.39, 95% confidence interval 0.16-0.96, P=0.040), although this did not translate into increased rapid viral response or sustained viral response (Prvr=0.93, Psvr=0.22).
CONCLUSION:
We have confirmed a strong association between functional ITPA variants and RBV-induced hemolysis and showed protection from RBV dose reduction, although this did not translate into increased rapid viral response or sustained viral response. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2608835
- author
- Eskesen, Arne Nørgaard ; Melum, Espen ; Moghaddam, Amir ; Bjøro, Kristian ; Verbaan, Hans LU ; Ring-Larsen, Helmer and Dalgard, Olav
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Gastroenterology and Hepathology
- volume
- 24
- issue
- 8
- pages
- 890 - 896
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000306289300004
- pmid:22584257
- scopus:84864041176
- ISSN
- 1473-5687
- DOI
- 10.1097/MEG.0b013e3283546efd
- language
- English
- LU publication?
- yes
- id
- 9b75cc90-c47a-4872-aded-44a5a4148657 (old id 2608835)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22584257?dopt=Abstract
- date added to LUP
- 2016-04-01 10:49:35
- date last changed
- 2022-01-26 02:49:44
@article{9b75cc90-c47a-4872-aded-44a5a4148657,
abstract = {{OBJECTIVES: <br/><br>
Two functional genetic variants in the inosine triphosphatase (ITPA) gene have been shown to be strongly associated with protection from ribavirin (RBV)-induced hemolysis. We aimed at evaluating this finding in a chronic hepatitis C genotype 2/3 cohort with a predominance of genotype 3 patients where available data are scarce. A second objective was to determine whether a protective association translated into the need for RBV reduction and hence a possible impact on treatment response. <br/><br>
<br/><br>
METHODS: <br/><br>
Overall, 457 patients were recruited from two trials of genotype 2/3 patients treated with pegylated interferon α-2b and weight-based RBV. rs1127354 and rs7270101 were genotyped and a composite ITPAase deficiency variable was graded according to the two single nucleotide polymorphisms. The primary endpoints were hemoglobin (Hb) decline from baseline and Hb decline of more than 3 g/dl at week 4. <br/><br>
<br/><br>
RESULTS: <br/><br>
Both single nucleotide polymorphisms and the composite ITPAase deficiency variable were strongly and independently associated with protection from a decline in Hb at week 4 in multivariate linear regression models (Prs1127354=7.0×10, Prs7270101=0.0036, PITPase deficiency variable =6.3×10). Patients with any degree of reduced ITPAase activity were less likely to have their RBV dose reduced (odds ratio 0.39, 95% confidence interval 0.16-0.96, P=0.040), although this did not translate into increased rapid viral response or sustained viral response (Prvr=0.93, Psvr=0.22). <br/><br>
<br/><br>
CONCLUSION: <br/><br>
We have confirmed a strong association between functional ITPA variants and RBV-induced hemolysis and showed protection from RBV dose reduction, although this did not translate into increased rapid viral response or sustained viral response.}},
author = {{Eskesen, Arne Nørgaard and Melum, Espen and Moghaddam, Amir and Bjøro, Kristian and Verbaan, Hans and Ring-Larsen, Helmer and Dalgard, Olav}},
issn = {{1473-5687}},
language = {{eng}},
number = {{8}},
pages = {{890--896}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{European Journal of Gastroenterology and Hepathology}},
title = {{Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort.}},
url = {{http://dx.doi.org/10.1097/MEG.0b013e3283546efd}},
doi = {{10.1097/MEG.0b013e3283546efd}},
volume = {{24}},
year = {{2012}},
}