ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C

被引：376

作者：

Fellay, Jacques ^{[1
]}

Thompson, Alexander J. ^{[2
,3
]}

Ge, Dongliang ^{[1
]}

Gumbs, Curtis E. ^{[1
]}

Urban, Thomas J. ^{[1
]}

Shianna, Kevin V. ^{[1
]}

Little, Latasha D. ^{[1
]}

Qiu, Ping ^{[4
]}

Bertelsen, Arthur H. ^{[4
]}

Watson, Mark ^{[4
]}

Warner, Amelia ^{[4
]}

Muir, Andrew J. ^{[2
,3
]}

Brass, Clifford ^{[4
]}

Albrecht, Janice ^{[4
]}

Sulkowski, Mark ^{[5
]}

McHutchison, John G. ^{[2
,3
]}

Goldstein, David B. ^{[1
]}

机构：

[1] Duke Univ, Ctr Human Genome Variat, Inst Genome Sci & Policy, Durham, NC 27708 USA

[2] Duke Univ, Div Gastroenterol, Sch Med, Div Gastroenterol, Durham, NC 27705 USA

[3] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA

[4] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

[5] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA

来源：

NATURE | 2010年 / 464卷 / 7287期

基金：

英国医学研究理事会;

关键词：

TRIPHOSPHATE PYROPHOSPHOHYDROLASE DEFICIENCY; NONSPHEROCYTIC HEMOLYTIC-ANEMIA; WHOLE-GENOME ASSOCIATION; INOSINE TRIPHOSPHATASE; HEXOKINASE DEFICIENCY; MISSENSE MUTATION; POPULATION; PHENOTYPE; RIBAVIRIN;

D O I：

10.1038/nature08825

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Chronic infection with the hepatitis C virus (HCV) affects 170 million people worldwide and is an important cause of liver-related morbidity and mortality(1). The standard of care therapy combines pegylated interferon (pegIFN) alpha and ribavirin (RBV), and is associated with a range of treatment-limiting adverse effects(2). One of the most important of these is RBV-induced haemolytic anaemia, which affects most patients and is severe enough to require dose modification in up to 15% of patients. Here we show that genetic variants leading to inosine triphosphatase deficiency, a condition not thought to be clinically important, protect against haemolytic anaemia in hepatitis-C-infected patients receiving RBV.

引用

页码：405 / 408

页数：4

共 27 条

[1] A haplotype map of the human genome
Altshuler, D
Brooks, LD
Chakravarti, A
Collins, FS
Daly, MJ
Donnelly, P
Gibbs, RA
Belmont, JW
Boudreau, A
Leal, SM
Hardenbol, P
Pasternak, S
Wheeler, DA
Willis, TD
Yu, FL
Yang, HM
Zeng, CQ
Gao, Y
Hu, HR
Hu, WT
Li, CH
Lin, W
Liu, SQ
Pan, H
Tang, XL
Wang, J
Wang, W
Yu, J
Zhang, B
Zhang, QR
Zhao, HB
Zhao, H
Zhou, J
Gabriel, SB
Barry, R
Blumenstiel, B
Camargo, A
Defelice, M
Faggart, M
Goyette, M
Gupta, S
Moore, J
Nguyen, H
Onofrio, RC
Parkin, M
Roy, J
Stahl, E
Winchester, E
Ziaugra, L
Shen, Y
[J]. NATURE, 2005, 437 (7063) : 1299 - 1320
[2] The ITPA c.94C>A and g.IVS2+21A>C sequence variants contribute to missplicing of the ITPA gene
Arenas, Monica
Duley, John
Sumi, Satoshi
Sanderson, Jeremy
Marinaki, Anthony
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2007, 1772 (01): : 96 - 102
[3] Analysis of ITPA phenotype-genotype correlation in the Bulgarian population revealed a novel gene variant in Exon 6
Atanasova, Srebrena
Shipkova, Maria
Svinarov, Dobrin
Mladenova, Antoaneta
Genova, Mariana
Wieland, Eberhard
Oellerich, Michael
von Ahsen, Nicolas
[J]. THERAPEUTIC DRUG MONITORING, 2007, 29 (01) : 6 - 10
[4] Pharmacogenetic significance of inosine triphosphatase
Bierau, Jorgen
Lindhout, Martijn
Bakker, Jaap A.
[J]. PHARMACOGENOMICS, 2007, 8 (09) : 1221 - 1228
[5] Genetic Variant m HK1 Is Associated With a Proanemic State and A1C but Not Other Glycemic Control-Related Traits
Bonnefond, Amelie
Vaxillaire, Martine
Labrune, Yann
Lecoeur, Cecile
Chevre, Jean-Claude
Bouatia-Naji, Nabila
Cauchi, Stephane
Balkau, Beverley
Marre, Michel
Tichet, Jean
Riveline, Jean-Pierre
Hadjadj, Samy
Gallois, Yves
Czernichow, Sebastien
Hercberg, Serge
Kaakinen, Marika
Wiesner, Susanne
Charpentier, Guillaume
Levy-Marchal, Claire
Elliott, Paul
Jarvelin, Marjo-Riitta
Horber, Fritz
Dina, Christian
Pedersen, Oluf
Sladek, Robert
Meyre, David
Froguel, Philippe
[J]. DIABETES, 2009, 58 (11) : 2687 - 2697
[6] DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency
Cao, HN
Hegele, RA
[J]. JOURNAL OF HUMAN GENETICS, 2002, 47 (11) : 620 - 622
[7] First mutation in the red blood cell-specific promoter of hexokinase combined with a novel missense mutation causes hexokinase deficiency and mild chronic hemolysis
de Vooght, Karen M. K.
van Solinge, Wouter W.
van Wesel, Annet C.
Kersting, Sabina
van Wijk, Richard
[J]. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2009, 94 (09): : 1203 - 1210
[8] Rare Variants Create Synthetic Genome-Wide Associations
Dickson, Samuel P.
Wang, Kai
Krantz, Ian
Hakonarson, Hakon
Goldstein, David B.
[J]. PLOS BIOLOGY, 2010, 8 (01)
[9] INDIVIDUAL VARIATION IN INOSINE TRIPHOSPHATE ACCUMULATION IN HUMAN ERYTHROCYTES
FRASER, JH
MEYERS, H
HENDERSON, JF
BROX, LW
MCCOY, EE
[J]. CLINICAL BIOCHEMISTRY, 1975, 8 (06) : 353 - 364
[10] Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium
Ganesh, Santhi K.
Zakai, Neil A.
van Rooij, Frank J. A.
Soranzo, Nicole
Smith, Albert V.
Nalls, Michael A.
Chen, Ming-Huei
Kottgen, Anna
Glazer, Nicole L.
Dehghan, Abbas
Kuhnel, Brigitte
Aspelund, Thor
Yang, Qiong
Tanaka, Toshiko
Jaffe, Andrew
Bis, Joshua C. M.
Verwoert, Germaine C.
Teumer, Alexander
Fox, Caroline S.
Guralnik, Jack M.
Ehret, Georg B.
Rice, Kenneth
Felix, Janine F.
Rendon, Augusto
Eiriksdottir, Gudny
Levy, Daniel
Patel, Kushang V.
Boerwinkle, Eric
Rotter, Jerome I.
Hofman, Albert
Sambrook, Jennifer G.
Hernandez, Dena G.
Zheng, Gang
Bandinelli, Stefania
Singleton, Andrew B.
Coresh, Josef
Lumley, Thomas
Uitterlinden, Andre G.
vanGils, Janine M.
Launer, Lenore J.
Cupples, L. Adrienne
Oostra, Ben A.
Zwaginga, Jaap-Jan
Ouwehand, Willem H.
Thein, Swee-Lay
Meisinger, Christa
Deloukas, Panos
Nauck, Matthias
Spector, Tim D.
Gieger, Christian
[J]. NATURE GENETICS, 2009, 41 (11) : 1191 - U48

← 1 2 3 →