This case-control study performed in a US clinical sample of heavy drinkers, replicates the previously reported association between ALD and rs738409 polymorphism in the PNPLA3 gene in heavy drinkers.
The rs738409 in the PNPLA3 gene was found to be significantly associated with ALD in allele and genotype frequencies (p = 6.25 × 10<sup>-14</sup> and p = 9.05 × 10<sup>-13</sup>).
Translation of candidates from these studies into ALD has established a role for variants in genes including PNPLA3 and potentially TM6SF2 across the disease spectrum from steatosis, through cirrhosis to hepatocellular carcinoma.
We performed a systematic review of previous studies on the relationship between rs738409 of PNPLA3 and ALD and meta-analysis was conducted in a random-effects model.
The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with non-alcoholic fatty liver disease and alcoholic liver disease (ALD).
Further prospective studies are required to confirm these results and to evaluate the potential of PNPLA3 as both a predictor and a therapeutic target in ALD.