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PNPLA3 polymorphism increases risk of alcoholic liver disease

Variants in the PNPLA3 gene are associated with increased risk for the entire spectrum of alcoholic liver disease, according to data published in the American Journal of Gastroenterology.

Researchers, including Ashwani Singal, MD, MS, of the division of gastroenterology and hepatology, University of Alabama, analyzed data collected from the PubMed/Medline, Embase and Cochrane databases. All studies looked at the PNPLA3 association with the entire spectrum of ALD, including alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC) and HCC.

Ashwani Singal

The specific study end points were ALF, ALI, AC or HCC among drinkers compared with healthy controls and the severity of ALD among drinkers. The main goal of the research was to examine the association of PNPLA3 polymorphisms with a predisposition for ALD, according to the research.

Ten studies with a total of 4,112 patients were included for the meta-analysis and each reported PNPLA3 polymorphism data on AC. Four studies each reported on ALI and HCC and one study reported data on AFL. Of the 10 studies, seven had recruited healthy controls compared to the other three that had no control group for comparison.

Among the 10 studies, the odds ratio (OR) for rs738409 CG genotype and GG genotype among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.5-3.28), respectively, compared with CC genotype. The OR for AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.1) and 12.41 (6.99-22.03), according to the research.

The research further stated that among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver patients. OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.6). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively.

“The PNPLA3 rs738409 polymorphism is associated with increased risk for the entire spectrum of ALD among drinkers, and increased propensity for AC and HCC in ALI patients,” the researchers concluded. “Studies are needed to clarify the association of PNPLA3 and steatosis in alcohol drinkers. The PNPLA3 gene may potentially be a therapeutic target in ALD and in the selection of donor organs for transplantation of patients with ALD.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.