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LMNA R644C associates with hepatic steatosis in a large cohort and increases cellular lipid droplet accumulation in vitro

Upadhyay, K. K.; Du, X.; Chen, Y.; Speliotes, E. K.; Brady, G. F.

2023-12-22 genetic and genomic medicine
10.1101/2023.12.20.23300290 medRxiv
Show abstract

The R644C variant of lamin A is controversial, as it has been linked to multiple phenotypes in familial studies, but has also been identified in apparently healthy volunteers. Here we present data from a large midwestern US cohort showing that this variant associates genetically with hepatic steatosis, and with related traits in additional publicly available datasets, while in vitro testing demonstrated that this variant increased cellular lipid droplet accumulation. Taken together, these data support this LMNA variants potential pathogenicity in lipodystrophy and metabolic liver disease.

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