RT Journal
A1 Liu, Hong-Hsing
A1 Lu, Peng
A1 Guo, Yingying
A1 Farrell, Erin
A1 Zhang, Xun
A1 Zheng, Ming
A1 Bosano, Betty
A1 Zhang, Zhaomei
A1 Allard, John
A1 Liao, Guochun
A1 Fu, Siyu
A1 Chen, Jinzhi
A1 Dolim, Kimberly
A1 Kuroda, Ayako
A1 Usuka, Jonathan
A1 Cheng, Janet
A1 Tao, William
A1 Welch, Kevin
A1 Liu, Yanzhou
A1 Pease, Joseph
A1 de Keczer, Steve A.
A1 Masjedizadeh, Mohammad
A1 Hu, Jing-Shan
A1 Weller, Paul
A1 Garrow, Tim
A1 Peltz, Gary
T1 An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity
JF Genome Research 
JO Genome Research 
YR 2010 
FD January 01 
VO 20 
IS 1 
SP 28 
OP 35 
DO 10.1101/gr.097212.109 
UL http://genome.cshlp.org/content/20/1/28.abstract 
AB Acetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple inbred mouse strains, along with knowledge-based filtering of these data, identified betaine-homocysteine methyltransferase 2 (Bhmt2) as a diet-dependent genetic factor that affected susceptibility to acetaminophen-induced liver toxicity in mice. Through an effect on methionine and glutathione biosynthesis, Bhmt2 could utilize its substrate (S-methylmethionine [SMM]) to confer protection against acetaminophen-induced injury in vivo. Since SMM is only synthesized in plants, Bhmt2 exerts its beneficial effect in a diet-dependent manner. Identification of Bhmt2 and the affected biosynthetic pathway demonstrates how a novel method of integrative genomic analysis in mice can provide a unique and clinically applicable approach to a major public health problem.