Study shows synergistic association between genetic and behavioral risks of liver disease

Excessive alcohol consumption and obesity are known to increase the risk of developing cirrhosis and liver cancer, but the risk is not the same for all people with these factors. Researchers from Baylor College of Medicine have found that a key genetic variant risk factor, PNPLA3, plays a synergistic role in increasing the risk of cirrhosis, liver cancer and liver-related death when it is associated with alcohol consumption and obesity. The results were published today in Open JAMA Network.

Researchers conducted a prospective study of over 400,000 people in the UK Biobank to assess whether PNPLA3 variant status could help stratify risk for obese heavy drinkers. The risk of liver disease increases with any of these factors, but the results showed a significantly increased risk when a person had all three.
The risk of developing cirrhosis was 17.5 times higher for people with all three risk factors, compared to 1.75 times higher for the PNPLA3 variant alone, 1.76 times higher for obesity alone and 2. 35 times higher for excessive alcohol consumption alone. The risk of developing liver cancer was 30.1 times higher and the risk of liver-related mortality was 21.8 times higher in people with all three risk factors.

“The PNPLA3 variant may be important in improving risk stratification for liver disease progression,” said Dr. Hyunseok Kim, first author of the study and a clinical researcher at Baylor at the time of the research. “For example, someone with the PNPLA3 variant might be more proactively counseled about drinking habits and body mass index. The person might also be a candidate for more preventative measures like more frequent screenings. or advanced imaging.

“Our study provides a unique opportunity to investigate the prognostic roles of PNPLA3, obesity, and excessive alcohol consumption in the risk of liver disease,” said co-corresponding author Dr Chris Amos. ‘study. Amos is Director of the Institute for Clinical and Translational Medicine, Professor of Medicine and Section Head of Epidemiology and Population Sciences, and Associate Director for Population and Quantitative Science at the Dan L Duncan Comprehensive Cancer Center at Baylor. “We don’t often see this kind of dramatic finding, so we’re excited about the clinical implications of these results.”

“Currently, patients are not routinely screened for this gene variant, but our results show that checking the status of this variant may be a useful risk stratification tool in liver disease surveillance,” said Dr. Fasiha Kanwal, corresponding co-author of the study. . Kanwal is Professor of Medicine, Section Head of Gastroenterology and Hepatology, and a Fellow of the Dan L Duncan Comprehensive Cancer Center at Baylor.

The research team said further study is needed to validate their findings in a different dataset. Their findings used data primarily from people of European descent. The researchers hope to find out if the results are similar in people of other ethnicities.

Other Baylor authors include Xiangjun Xiao, Dr. Jinyoung Byun, Dr. Aaron Thrift, and Dr. Hashem El-Serag. Dr. Goo Jun, Dr. Stacia M. DeSantis, and Dr. Han Chen of the University of Texas Health Sciences Center at Houston also contributed to this research. See the publication for a full list of funding for this research.

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