TY  - JOUR
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
Y1  - 2010/01/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 28 
EP  - 35 
DO  - 10.1101/gr.097212.109 
VL  - 20 
IS  - 1 
UR  - http://genome.cshlp.org/content/20/1/28.abstract 
N2  - 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. 
ER  -