Polymorphism of N-acetyltransferase 2 Gene and the Susceptibility to Alcoholic Liver Cirrhosis: Interaction With Smoking

Abstract

The genetic factor, NAT2 polymorphism, may interact with environmental factor, smoking, to confer different susceptibilities to ALC. NAT2 rapid acetylators with smoking habit may increase the risk of ALC in Chinese.

Sulfamethoxazole-trimethoprim-induced liver injury and genetic polymorphisms of NAT2 and CYP2C9 in Taiwan

“…Previous studies have shown that slow acetylators may metabolize some drugs and precarcinogens slowly, and hence are at a higher risk of antituberculosis DILI, alcoholic liver disease, hepatocellular carcinoma and many other cancers [5][6][7][8]. SMX-TMP is well known to induce hypersensitivity reactions, such as fever, eosinophilia, atypical lymphocytosis, skin rash and even Stevens-Johnson syndrome [2].…”

“…Genetic variations of NAT2 are responsible for N -acetylation polymorphisms, in which humans can be classified into normal, intermediate and slow acetylator phenotypes according to the presence of zero, one or two variant alleles [4]. Previous studies have shown that slow acetylators may metabolize some drugs and precarcinogens slowly, and hence are at a higher risk of antituberculosis DILI, alcoholic liver disease, hepatocellular carcinoma and many other cancers [5–8]. SMX-TMP is well known to induce hypersensitivity reactions, such as fever, eosinophilia, atypical lymphocytosis, skin rash and even Stevens–Johnson syndrome [2].…”

“…Its principle encoding gene, NAT2, is polymorphic and can affect the activity of NAT [4]. Previous studies from our groups and other centers have found associations between genetic variations of NAT2 and the risks of antituberculosis DILI [5], alcoholic liver cirrhosis [6], hepatocellular carcinoma [7] and many other diseases [8]. A few studies have revealed that NAT2 slow acetylators are apt to have SMX-related hypersensitivity reactions [9][10][11][12][13][14][15][16], whereas other studies have found no such association [17][18][19][20][21][22][23][24].…”

Role of N-acetyltransferase 2 gene polymorphism in the human pathology

“…В литературе представлены противоречивые данные о роли полиморфизма NAT2 в развитии цирроза печени. Наибольшее количество публикаций касается развития цирроза, обусловленного действием изониазида в стандартной дозировке, когда частота побочных эффектов, включая развитие хронического гепатита, значительно выше у медленных ацетиляторов [2,23,24,67 [69]. Данные выводы согласуются с результатами предыдущих исследований российских учёных о связи фенотипа NAT2 с развитием и течением хронических заболеваний печени, где было показано, что быстрые ацетиляторы обладают высокой предрасположенностью к развитию хронических заболеваний печени с последующей трансформацией в цирроз [70].…”