ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C.
Chronic infection with the hepatitis C virus (HCV) affects 170 million people worldwide and is an important cause of liver-related morbidity and mortality. The standard of care therapy combines pegylated interferon (pegIFN) alpha and ribavirin (RBV), and is associated with a range of treatment-limiting adverse effects. 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.
Fellay
Jacques
J
Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA.
Thompson
Alexander J
AJ
Ge
Dongliang
D
Gumbs
Curtis E
CE
Urban
Thomas J
TJ
Shianna
Kevin V
KV
Little
Latasha D
LD
Qiu
Ping
P
Bertelsen
Arthur H
AH
Watson
Mark
M
Warner
Amelia
A
Muir
Andrew J
AJ
Brass
Clifford
C
Albrecht
Janice
J
Sulkowski
Mark
M
McHutchison
John G
JG
Goldstein
David B
DB
D000483:Alleles; D000743:Anemia, Hemolytic / Q000139:chemically induced* / Q000150:complications / Q000235:genetics*; D000998:Antiviral Agents; D002890:Chromosomes, Human, Pair 20; D005060:Europe / Q000208:ethnology; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006454:Hemoglobins / Q000172:deficiency / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011755:Pyrophosphatases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D044469:Racial Groups / Q000235:genetics; D012254:Ribavirin / Q000627:therapeutic use; D014481:United States; D000097630:Inosine Triphosphatase
D000998:Antiviral Agents; D006454:Hemoglobins; D011755:Pyrophosphatases; D012254:Ribavirin; D000097630:Inosine Triphosphatase; C511829:ITPA protein, human