A “mild” form of lysosomal acid lipase deficiency (LAL-D) may exist and could play a role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), according to a new study published in the journal Pharmacology Research and Perspective.

This “mild” form may be associated with the single nucleotide polymorphism (SNP) rs1051338 in the lysosomal acid type (LIPA) gene, which encodes the lysosomal acid LIPAse enzyme that catalyzes triglycerides and hydrolyses cholesterol esters in lysosomes. People carrying this rare allele may be at an increased risk of nonalcoholic steatohepatitis.

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“The clinical characterization of the rs1051338 polymorphism can provide useful prognostic data as well as a better diagnostic classification,” the study authors wrote. “The study of genetic background of fatty liver and NAFLD could lead to better therapeutic strategies soon.”

Their aim was to evaluate the impact of the rare allele on lipid phenotype, the severity of fat in the liver, and LAL activity in patients with dyslipidemia associated with NAFLD.

They analyzed 74 patients with hypoalphalipoproteinemia or mixed hyperlipemia in terms of their transaminases, LAL activity, and rs1051338 SNP genotype.

They found that patients with the rare rs1051338 allele had higher levels of triglycerides and liver transaminase and lower levels of high-density lipoprotein cholesterol (HDL-C). Using statistical analyses, the researchers also showed there was an independent association between the rs1051338 SNP and the severity of fat in the liver in people with NAFLD.

They concluded that the rare allele may modulate the severity of fat in the liver as well as that of atherogenic dyslipidemia in patients with NAFLD in a way similar to what is seen in LAL-D.

“These results should be confirmed by further studies, which could finally define rs1051338 functional nature and the existence of ‘mild’ forms of LAL-D that could play an important role in NAFLD pathogenesis,” they wrote.


Pasta A, Borro P, Cremonini AL, et al. Effect of a common missense variant in LIPA gene on fatty liver disease and lipid phenotype: new perspectives from a single-center observational study. Pharmacol Res Perspect. 2021;9(5):e00820. doi:10.1002/prp2.820