PhD Scientific Days 2025

Poster Session I. - A: Molecular Medicine

Regulatory Insights into ZDHHC19 in Sepsis

Name of the presenter

Maricza Katalin

Institute/workplace of the presenter

Department of Molecular Biology, Semmelweis University

Authors

Dr. Katalin Maricza¹, Dr. Zsuzsanna Molnár¹

1: Department of Molecular Biology, Semmelweis University

Text of the abstract

Introduction: Sepsis is a life-threatening systemic inflammatory response triggered by infection and remains a leading cause of mortality worldwide. Due to its rapid progression, identifying early diagnostic and prognostic molecular biomarkers is crucial. The ZDHHC19 gene, encoding an S-palmitoyltransferase, has emerged as a potential biomarker, but its regulation—particularly by microRNAs and genetic variants—remains poorly understood.

Aims: We aimed to analyze ZDHHC19 mRNA expression in sepsis and its relationship with two predicted regulatory microRNAs (miR-4733-3p, miR-596). We also assessed the potential effects of two 3'UTR SNPs (rs112579116, rs2293161) on miRNA binding. ZDHHC19 expression was tracked longitudinally in one recovering septic patient. Based on these findings, we examined ZDHHC gene family expression during recovery in six patients using RNA-seq.

Methods: We enrolled 146 patients, including 63 with sepsis. RNA was isolated from peripheral blood, and RT-qPCR was used to quantify gene and miRNA expression. SNPs were genotyped via TaqMan-PCR. Reference genes were selected using NormFinder. SPSS was used for statistics; FDR correction was applied. ZDHHC19 expression was monitored in one patient during recovery, and RNA-seq analysis of the full ZDHHC family was performed in six additional cases.

Results: ZDHHC19 expression was significantly elevated in sepsis, especially in urogenital infections. Both miRNAs showed decreased levels, inversely correlating with ZDHHC19. Expression was positively associated with PCT, neutrophils, and INR. SNPs showed no link to expression or clinical parameters. In the recovering patient, ZDHHC19 closely followed clinical improvement and SOFA score. Among six NGS-analyzed patients, ZDHHC19 showed the most pronounced recovery-related change.

Conclusion: Our findings support ZDHHC19 as a promising molecular marker in sepsis, with expression reflecting disease severity and clinical course. While microRNAs may modulate its expression, the studied SNPs appear to have a limited functional impact. Further functional studies are warranted.

Funding: This study was supported by the National Research, Development and Innovation Office (K-131680) and Semmelweis University (STIA-18-KF/M).