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Observational Study
. 2021 Oct;9(5):e00820.
doi: 10.1002/prp2.820.

Effect of a common missense variant in LIPA gene on fatty liver disease and lipid phenotype: New perspectives from a single-center observational study

Andrea Pasta  1 , Paolo Borro  2 , Anna Laura Cremonini  3 , Elena Formisano  4 , Giulia Tozzi  5 , Stefano Cecchi  6 , Raffaele Fresa  1 , Sara Labanca  2 , Afscin Djahandideh  2 , Samir Giuseppe Sukkar  3 , Antonino Picciotto  1   2 , Livia Pisciotta  1   3
Affiliations
Observational Study

Effect of a common missense variant in LIPA gene on fatty liver disease and lipid phenotype: New perspectives from a single-center observational study

Andrea Pasta et al. Pharmacol Res Perspect. 2021 Oct.

Abstract

Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disease characterized by hypoalphalipoproteinemia, mixed hyperlipemia, and fatty liver (FL) due to mutations in LIPAse A, lysosomal acid type (LIPA) gene. The rs1051338 single-nucleotide polymorphism (SNP) in LIPA gene, in vitro, could adversely affect the LAL activity (LAL-A). Nonalcoholic fatty liver disease (NAFLD) is often associated with metabolic syndrome, and the diagnosis requires the exclusion of excess of alcohol intake and other causes of hepatic disease. The aim of the study was to evaluate the impact of rs1051338 rare allele on lipid phenotype, severity of FL, and LAL-A in patients suffering from dyslipidemia associated with NAFLD. We selected 74 subjects with hypoalphalipoproteinemia or mixed hyperlipemia and evaluated transaminases, liver assessment with controlled attenuation parameter (CAP), LAL-A, rs1051338 SNP genotype. The presence of rare allele caused higher levels of triglycerides and hepatic transaminase and lower levels of high-density lipoprotein cholesterol (HDL-C). Multivariate analysis highlighted independent association between rare allele and FL severity in subjects with NAFLD. The rs1051338 SNP may modulate FL severity and atherogenic dyslipidemia in patients suffering from NAFLD.

Keywords: LIPA gene; NAFLD; controlled attenuation parameter; hepatic steatosis; rs1051338.

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Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Figures

FIGURE 1
FIGURE 1
(A) Age, (B) BMI, (C) TC, (D) HDL‐C, (E) LDL‐C, (F) TG, (G) Glycemia, (H) AST, (I) ALT, (L) LAL‐A, (M) CAP, (N) VCTE,and (O) SWE levels in different rs1051338 SNP genotypes. BMI, Body mass index; LAL‐A, Lysosomal acid lipase activity; SWE, Two‐dimensional shear wave elastography; CAP, Controlled attenuation parameter; VCTE, FibroScan® Vibration‐controlled transient elastography. **p < .01 for Wilcoxon–Mann–Whitney test. *p < .05 for Wilcoxon–Mann–Whitney test
FIGURE 2
FIGURE 2
Forrest‐Plot of the multivariate (A) ordinal regression analysis for the different stages of steatosis and (B) logistic regression analysis S0, 1, 2 vs S3. BMI, Body Mass Index; F, female; p, p‐value
See this image and copyright information in PMC

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