The aldehyde dehydrogenase-2 polymorphism affects alcohol dependence differently by gender

August 15, 2011

Researchers know that gender differences exist in the prevalence, characteristics, and course of alcohol dependence (AD). Polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are strong genetic determinants of AD. A new study of gender differences in the effects of these polymorphisms on the development of AD has found that inactive ALDH2 can accelerate the development of AD in women.

Results will be published in the November 2011 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

" (AD) is much more common among males than females," said Mitsuru Kimura, chief scientist in the department of psychiatry at the Kurihama Alcoholism Center in Japan as well as corresponding author for the study. "However, female alcoholics are more likely to have co-existing psychiatric disorders than male patients."

Victor Hesselbrock, professor of psychiatry at the University of Connecticut School of Medicine, concurred. "Females with AD typically have a greater prevalence of affective problems such as depression and anxiety than males, while males with AD typically display more associated behavioral problems – including antisocial personality disorder – and have higher rates of co-morbid drug problems," he said. "In general, females have a later onset of AD but typically come to treatment earlier than males. More recently, however, trends indicate that females born in more recent birth cohorts – after 1970 or so – are looking more like males in their clinical picture, for example, age of onset of drinking behaviors, including onset of dependence, and associated problems, including drug problems. Usually have been attributed to differences in size, such as body mass, body water and/or exposure to alcohol. None of these previous studies ever considered any genotypic information, such as ADH1B or ALDH, as possible explanations for gender differences."

"The two we examined are the most evident genetic determinants of the disease," said Kimura. "ADH1B and ALDH2 eliminate most of the alcohol taken into the body. A lack of ALDH2 activity causes a 'flushing response' which includes flushing, nausea, and a headache after drinking, so it tends to greatly suppress people's drinking."

"ADH is important for the initial metabolism of ethanol into acetaldehyde, while ALDH is important for metabolizing acetaldehyde, the first by-product of ethanol metabolism, into acetate and water," said Hesselbrock. "A variant of the ALDH gene, ALDH2*2 … is relatively common in select Asian populations, approaching 50 percent, but is absent in the homozygous form in Caucasian populations. The allele frequency of these two polymorphisms does not vary by gender."

Kimura and his colleagues examined 615 individuals (415 men, 200 women) hospitalized for AD in the Kurihama Alcoholism Center. Clinical information and background data were gleaned from chart reviews, and ALDH2 and ADH1B genotyping were performed.

Results indicated that ALDH2 polymorphisms appear to have contrasting effects on the development of AD among men and women. While females typically cannot drink as much as males because of their smaller body size, current findings suggest that differences in alcohol metabolism due to genetic factors may also help explain morbidity differences both between and within genders apart from their different levels of drinking.

"Usually the painful experience of flushing response caused by inactive ALDH2 suppresses alcohol drinking," said Kimura, "but our findings suggest that women who have co-existing psychiatric disorders might be motivated to drink heavily in order to cope with the symptoms of their psychiatric disorders." This suggests a "gene-gender interaction" in the development of AD, meaning that the same genetic factor has a different effect on the different genders.

"In addition, our results might suggest female AD has two types: one is characterized by early-onset and a high prevalence of psychiatric comorbidity; the other by late-onset and a relatively low prevalence of psychiatric comorbidity," said Kimura. "The early-onset subtype likely has a primary psychiatric disorder, and the psychiatric comorbidity likely caused secondary alcohol-related problems. In this subtype, alcohol consumption is scarcely suppressed by the flushing response induced by inactive ALDH2. On the other hand, the middle- or late-onset subtype likely has AD as primary with a low prevalence of psychiatric comorbidity. This subtype commonly increases consumption to reduce stress or to enjoy social activities, and results in AD. This subtype is more similar to the pattern of male AD and is suppressed by inactive ALDH2."

"This study demonstrates that some genotypes may also be useful phenotypes," said Hesselbrock, "helping us to better describe and understand variations in the expression of alcoholism between patients and possibly provide clues to the clinical course. Furthermore, these findings, if replicated, could be quite useful for the clinician. Currently clinicians have no objective biological variables available for use in helping them diagnose and develop treatment plans for patients. Additional studies may identify differences in the course of alcoholism or differences in treatment response to certain medications based upon these genotypes."

Explore further: Increase in risk of certain gastric cancer from heavy drinking

Related Stories

Increase in risk of certain gastric cancer from heavy drinking

May 18, 2011
The results from a very well-done meta-analysis support other data generated on the risk of alcohol consumption and gastric cancer – that is – that the risk may be real for heavy alcohol consumption but not for ...

Recommended for you

Exploring the potential of human echolocation

June 25, 2017
People who are visually impaired will often use a cane to feel out their surroundings. With training and practice, people can learn to use the pitch, loudness and timbre of echoes from the cane or other sounds to navigate ...

Team eradicates hepatitis C in 10 patients following lifesaving transplants from infected donors

April 30, 2017
Ten patients at Penn Medicine have been cured of the Hepatitis C virus (HCV) following lifesaving kidney transplants from deceased donors who were infected with the disease. The findings point to new strategies for increasing ...

'bench to bedside to bench': Scientists call for closer basic-clinical collaborations

March 24, 2017
In the era of genome sequencing, it's time to update the old "bench-to-bedside" shorthand for how basic research discoveries inform clinical practice, researchers from The Jackson Laboratory (JAX), National Human Genome Research ...

The ethics of tracking athletes' biometric data

January 18, 2017
(Medical Xpress)—Whether it is a FitBit or a heart rate monitor, biometric technologies have become household devices. Professional sports leagues use some of the most technologically advanced biodata tracking systems to ...

Financial ties between researchers and drug industry linked to positive trial results

January 18, 2017
Financial ties between researchers and companies that make the drugs they are studying are independently associated with positive trial results, suggesting bias in the evidence base, concludes a study published by The BMJ ...

Best of Last Year – The top Medical Xpress articles of 2016

December 23, 2016
(Medical Xpress)—It was a big year for research involving overall health issues, starting with a team led by researchers at the UNC School of Medicine and the National Institutes of Health who unearthed more evidence that ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.