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Multiple variants in LGALS9 show increased risk for ALD

In a genetic analysis of heavy consumers of alcohol, researchers found the rs4239242 and rs4794976 polymorphisms in gene encoding LGALS9 were associated with an increased risk for developing alcoholic liver disease.

“Alcohol consumption is a major cause of chronic liver disease and contributes to a large proportion of cirrhosis-related deaths worldwide,” the researchers wrote. “However, only a fraction of heavy consumers of alcohol develop advanced alcoholic liver disease, so there are likely to be other risk factors.”

To determine other risk factors, researchers analyzed isolated DNA from peripheral mononuclear blood cells (PMBCs) of 554 European patients who consumed more than 80 g of ethanol per day and had no other risk factors for chronic liver disease. Polymorphisms in the gene encoding LGALS9, a well-known gene previously shown to mediate liver injury, were examined, according to the research.

“Select LGALS9 polymorphisms were genotyped using allelic discrimination. We also genotyped and measured expression of LGALS9 messenger RNA in PBMCs from individuals who were not heavy consumers of alcohol,” the researchers wrote.

Overall, 375 patients had alcoholic liver disease (ALD) and 179 had normal liver function with no evidence of liver disease. Of the patients with ALD, 268 had cirrhosis and 74 had alcoholic hepatitis.

When researchers looked for single-nucleotide polymorphisms (SNPs) in patients with liver disease compared with patients without liver disease, four SNPs were found to be associated with an increased risk for developing ALD (rs3751093, rs4239242, rs732222, and rs4794976).

“We found that levels of LGALS9 messenger RNA and protein expressed were associated with an allele carried by PMBCs,” the researchers wrote.

Multivariate analysis also showed that rs4239242 and rs4794976 were associated with an increased risk for ALD.

The researchers concluded: “The LGALS9 sequence variations reported here may provide predictive information regarding the risk of developing ALD in at-risk individuals and identify novel therapeutic targets for this common disease.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.