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

被引：377

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

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