LDLR and APOB pathogenic variants predict discordant TSH effect on LDL-C

Area of Science:

• Endocrinology
• Lipid Metabolism
• Genetics

Background:

• Thyroid hormones are crucial for lipoprotein metabolism, mainly via LDL receptor regulation.
• The relationship between TSH and LDL-C in hypercholesterolemic children, considering FH status and gene defects, remains unclear.

Purpose of the Study:

• To investigate TSH-lipid associations in prepubertal children.
• To determine if FH status or specific gene variants (LDLR vs. APOB) modify these associations.

Main Methods:

• Cross-sectional study of 738 prepubertal children from a Slovenian tertiary center.
• Included universal FH screening, cascade screening, TSH, fasting lipid measurements, and genetic testing (LDLR, APOB, PCSK9 variants).

Main Results:

• TSH did not correlate with lipids in the overall cohort, except for triglycerides in males.
• In FH-positive children, TSH correlated positively with total cholesterol, LDL-C, and ApoB.
• A significant TSH-LDL-C association was observed in LDLR variant carriers but not in APOB carriers.

Conclusions:

• TSH is positively associated with LDL-C specifically in familial hypercholesterolemia caused by LDLR variants.
• Genetic background appears to influence hormonal sensitivity in lipid regulation.
• Monitoring thyroid status may be particularly important for individuals with LDLR-related FH.