Steatotic Liver Disease Predicts Lower Likelihood of LDLR Gene Mutations in Young Korean Patients with Suspected Familial Hypercholesterolemia.

BACKGROUND

Familial hypercholesterolemia (FH) is underdiagnosed in young adults, and universal genetic testing is costly. We evaluated whether steatotic liver disease (SLD) could predict low-density lipoprotein receptor (LDLR) mutations in suspected FH.

METHODS

We retrospectively analyzed 111 Korean military personnel aged 19-30 years who underwent LDLR sequencing and SLD assessment using controlled attenuation parameter (CAP) and hepatic steatosis index.

RESULTS

Pathogenic LDLR variants were identified in 23.4% of participants. Compared with non-carriers, carriers had lower CAP values (245.2 dB/m vs. 273.9 dB/m, P=0.085) and a significantly lower prevalence of SLD (52.9% vs. 82.0%, P=0.025). Multivariable logistic regression confirmed SLD was independently associated with lower odds of variant carriage (adjusted odds ratio, 0.11; 95% confidence interval, 0.02 to 0.56; P=0.009). Clustering analysis showed the highest variant prevalence in lean, non-SLD individuals.

CONCLUSION

SLD was inversely associated with genetically confirmed FH. Incorporating SLD assessment may help prioritize genetic testing in populations with a high prevalence of SLD or limited access to sequencing resources.