CREB3L3-Associated Hypertriglyceridemia: A Significant Contribution to the Spectrum of Monogenic Dyslipidemias in the Russian Population.

Introduction. Extreme hypertriglyceridemia (HTG) often has a hereditary nature. Besides the classic lipolysis genes (LPL, APOC2, APOA5), the significance of the transcription factor gene CREB3L3 remains understudied in the Russian population. Aim: to assess the contribution and characterize the clinical and laboratory features of CREB3L3-associated hypertriglyceridemia. Methods. A clinical and molecular examination of 103 patients with extreme HTG (triglyceride level >10 mmol/L) was conducted. Sequencing of the “Hereditary Hyperlipidemias” gene panel and whole-exome sequencing were used. For phenotypic assessment, the lipid profile and the diagnostic scale by Moulin et al. (2018) were applied. Results. A monogenic origin of HTG was confirmed in 24 patients (23.3%). The CREB3L3-associated form was identified in 9 individuals, accounting for 37.5% of all hereditary cases. Its phenotype differed from classical familial hyperchylomicronemia by a significantly higher HDL level (0.95 vs. 0.47 mmol/L, p<0.05) and a lower score on the Moulin scale (8 vs. 12, p<0.001). A recurring variant, c.733_738delinsGAAAAAT (p.Lys245GlufsTer130), was found in 66.7% of patients with CREB3L3-HTG, which is not registered in Russian population databases. Conclusion. CREB3L3 is the second most significant gene in the structure of monogenic hypertriglyceridemias in the Russian Federation. Its associated form has a distinctive laboratory profile, which is important for differential diagnosis. The identification of a frequent variant suggests the possibility of targeted screening. The inclusion of CREB3L3 in diagnostic panels for patients with extreme HTG is clinically justified.

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