Dataset Information

Extremely low levels of low-density lipoprotein potentially suggestive of familial hypobetalipoproteinemia: A separate phenotype of NAFLD?

ABSTRACT:

Background

Low-density lipoprotein cholesterol (LDL-C) levels below 50 mg/dL may suggest familial hypobetalipoproteinemia, particularly in patients with hepatic steatosis. The prevalence of hypobetalipoproteinemia in cohorts with nonalcoholic fatty liver disease (NAFLD) is not known, and it is not clear whether the severity of liver disease of these patients is different. The objective of this study was to address these questions in a large pediatric NAFLD cohort.

Methods

Retrospective study of children followed at the Steatohepatitis Center of a tertiary care center from August 2010 to October 2017. Patients with secondary causes of hepatic steatosis and those on statins were excluded.

Results

Of the 740 patients included, 58 (8%) had hypobetalipoproteinemia. These patients were younger (P = .04), had a lower body mass index (P < .01) and waist circumference (P = .01), and were less likely to be on metformin (P = .01). In spite of that, serum aminotransferase levels were not different between those with low, normal, and high LDL-C levels. Of the 222 patients who had both lipid and histology data available, the steatosis score was higher in those with low LDL-C compared to those with normal or elevated LDL-C, a result that trended toward significance (P = .06). The severity of inflammation and fibrosis did not differ between the groups. When all patients with hypertriglyceridemia were excluded, steatosis severity was higher in those with low LDL-C (P = .04).

Conclusion

Hypobetalipoproteinemia is common among patients with NAFLD and is associated with similar liver disease severity in spite of a leaner phenotype and a more favorable metabolic profile.

SUBMITTER: Mouzaki M

PROVIDER: S-EPMC8830607 | biostudies-literature | 2019 May - Jun

REPOSITORIES: biostudies-literature

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Publications

Extremely low levels of low-density lipoprotein potentially suggestive of familial hypobetalipoproteinemia: A separate phenotype of NAFLD?

Mouzaki Marialena M Shah Amy A Arce-Clachar Ana Catalina AC Hardy Jennifer J Bramlage Kristin K Xanthakos Stavra A SA

Journal of clinical lipidology 20190214 3

<h4>Background</h4>Low-density lipoprotein cholesterol (LDL-C) levels below 50 mg/dL may suggest familial hypobetalipoproteinemia, particularly in patients with hepatic steatosis. The prevalence of hypobetalipoproteinemia in cohorts with nonalcoholic fatty liver disease (NAFLD) is not known, and it is not clear whether the severity of liver disease of these patients is different. The objective of this study was to address these questions in a large pediatric NAFLD cohort.<h4>Methods</h4>Retrospe ...[more]

PMID: 30879942

Similar Datasets

Project description:BackgroundFamilial hypercholesterolemia (FH) is a common monogenic autosomal dominant disorder, primarily mainly caused by pathogenic mutations in the low-density lipoprotein receptor (LDLR) gene. Through phenotypic-genetic linkage analysis, two LDLR pathogenic mutations were identified in FH families: c.G1027A (p.Gly343Ser) and c.G1879A (p.Ala627Thr).Materials and methodsWhole exome sequencing was conducted on the proband with familial hypercholesterolemia to identify the target gene and screen for potential pathogenic mutations. The suspicious responsible mutation sites in 14 family members were analyzed using Sanger sequencing to assess genotype-phenotype correlations. Mutant and wild type plasmids were constructed and transfected into HEK293T cells to evaluate LDLR mRNA and protein expression. In parallel, bioinformatics tools were employed to predict structural and functional changes in the mutant LDLR.ResultsImmunofluorescence analysis revealed no significant difference in the intracellular localization of the p.Gly343Ser mutation, whereas protein expression of the p.Ala627Thr mutation was decreased and predominantly localized in the cytoplasm. Western blotting has showed that protein expression levels of the mutant variants were markedly declined in both cell lysates and supernatants. Enzyme linked immunosorbent assay has demonstrated that LDLR protein levels in the supernatant of cell culture medium was not significant different from those of the wild-type group. However, LDLR protein levels in the cell lysate of both the Gly343Ser and Ala627Thr variants groups were significantly lower than those in the wild-type group. Bioinformatic predictions further suggested that these mutations may affect post-translational modifications of the protein, providing additional insight into the mechanisms underlying the observed reduction in protein expression.ConclusionsIn this study, we identified two heterozygous pathogenic variants in the LDLR gene, c.G1027A (p.Gly343Ser) and c.G1879A (p.Ala627Thr), in a family with familial hypercholesterolemia. We also conducted preliminary investigations into the mechanisms by which these mutations contribute to disease pathology.

Dataset Information

Extremely low levels of low-density lipoprotein potentially suggestive of familial hypobetalipoproteinemia: A separate phenotype of NAFLD?

Background

Methods

Results

Conclusion

Publications

Extremely low levels of low-density lipoprotein potentially suggestive of familial hypobetalipoproteinemia: A separate phenotype of NAFLD?

Similar Datasets

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