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

Kafol, Jan (avtor), Šikonja, Jaka (avtor), Mlinarič, Matej (avtor), Čugalj Kern, Barbara (avtor), Pricop-Jeckstadt, Mihaela (avtor), Drole Torkar, Ana (avtor), Gorjanc, Tevž (avtor), Petek, Andraž (avtor), Lakner, Andreja (avtor), Kovač, Jernej (avtor), Battelino, Tadej (avtor), Grošelj, Urh (avtor)

Background and aims Thyroid hormones regulate lipoprotein metabolism—primarily by up-regulating the LDL receptor. Whether TSH relates to LDL-C in hypercholesterolemic children, and whether this depends on familial hypercholesterolemia (FH) status or the underlying defective gene, is uncertain. We evaluated TSH–lipid associations in prepubertal children and tested effect modification by FH status and, within FH, by gene with a pathogenic variant (LDLR vs APOB). Methods We performed a cross-sectional study of prepubertal children referred to the Slovenian national tertiary center through the universal FH screening program or cascade screening. Eligibility required concurrent TSH and fasting lipid measurement and completed genetic testing (pathogenic/likely pathogenic variants in LDLR/APOB/PCSK9 vs polygenic hypercholesterolemia). Results Among 738 children, 182 (24.7%) were FH-positive (LDLR 132; APOB 50). In the pooled cohort, TSH did not correlate with age or lipids (all p≥0.050). After sex stratification, TSH correlated with triglycerides only in males (ρ=0.156; p=0.012). In FH-positive children, TSH correlated with total cholesterol, LDL-cholesterol, and ApoB (ρ≈0.184–0.207; all p<0.050), with no associations in FH-negative children. Interaction testing confirmed effect modification by FH (TSH×FH β=0.141 mmol/L per mIU/L, p=0.023). Within FH-positive children, a positive TSH–LDL-C slope was seen in LDLR carriers (β=0.237, p=0.004) but not in APOB carriers (β=−0.065, p=0.655). Conclusions TSH was positively associated with LDL-C only in FH due to LDLR variants, not in APOB carriers. These findings suggest that genetic background may shape hormonal sensitivity, and that attention to thyroid status could be particularly relevant in LDLR-FH.

• Jezik: Angleški jezik
• Ključne besede: TSH, low-density lipoprotein cholesterol, familial hypercholesterolemia, LDLR, APOB, subclinical hypothyroidism
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 7 str.
• Številčenje: Vol. 415, art. 120672
• PID: 20.500.12556/RUL-183385
• UDK: 616.1:616-053.2
• ISSN pri članku: 1879-1484
• DOI: 10.1016/j.atherosclerosis.2026.120672
• COBISS.SI-ID: 268549379
• Datum objave v RUL: 12.06.2026

Gradivo je del revije

• Naslov: Atherosclerosis
• Skrajšan naslov: Atherosclerosis
• Založnik: Elsevier
• ISSN: 1879-1484
• COBISS.SI-ID: 23193093

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0343
• Naslov: Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: J3-2536
• Naslov: UGOTAVLJANJE GENETSKIH VZROKOV DISLIPIDEMIJ PRI OTROCIH IN MLADOSTNIKIH TER NJIHOVO ZGODNJE ODKRIVANJE S POPULACIJSKIM PRESEJANJEM