Low Alanine Aminotransferase Levels in Alcohol Consuming Male Subjects, Carriers of the Common ALDH2 Deficient Variant, ALDH2*2.

Alanine aminotransferase (ALT) is a commonly used indicator of hepatocellular injury in clinical liver disease practice. While a variety of factors influence serum ALT levels, we focus here on the effect of alcohol consumption on ALT levels in the context of the common East Asian aldehyde dehydrogenase 2 (ALDH2) dysfunctional polymorphism, ALDH2*2 (or rs671 E504K missense variant). ALDH2 plays a key role in the detoxification of alcohol-derived metabolite, acetaldehyde. Four of the five studies identified from a literature search showed that individuals with the ALDH2*1/*2 heterozygous genotypes had ALT levels below the normal range if they consume alcoholic beverages despite having only 10%-38% of the normal ALDH2 activity. This effect is consistent and more pronounced in men in studies from different East Asian populations. It is noteworthy that one large study showed that low ALT levels of ALDH2*1/*2 were also observed with excessive alcohol consumption, which is a common risk factor for alcohol-related liver disease (42 g ethanol per day in men). It is unclear if these lower-than-normal ALT levels indicate a hepatoprotective effect or if it is a missed clinical indicator of hepatic injury. As ALT levels in the general practice are used to diagnose potential liver disease, it is therefore necessary to determine whether alcohol-induced decline in ALT may mask the diagnosis of liver disease in an estimated 540 million carriers of the ALDH2*1/*2 genotypes in the East Asian ancestry group in clinical practice.