PhD Scientific Days 2024

Poster Session F - Molecular Medicine 3.

Molecular genetic study of ZDHHC19 gene in sepsis

Text of the abstract

Introduction: Palmitoylation is a special posttranslational modification because it is reversible and can be modulated by extracellular factors. The main S-palmitoyltransferases are the ZDHHC zinc finger proteins containing the enzymatic DHHC domain responsible for palmitoylation. In humans, the ZDHHC palmitoyltransferase family consists of 23 members, including ZDHHC19. This enzyme has several targets that affect cell movement and proliferation.

Aims: The aim of the present study was to investigate the expression of ZDHHC19 and that of microRNAs influencing its expression in sepsis. We also wanted to examine the association between SNPs affecting microRNA-based regulation and the disease.

Method: Peripheral blood samples (N = 166) were taken into TempusTM Blood RNA collection tubes. Total RNA was isolated using the MagMaxTM for Stabilized Blood Tubes RNA Isolation Kit. RNA was reverse transcribed into cDNA with the SuperScript VILO cDNA Synthesis Kit and with miRNA 1st-Strand cDNA Synthesis Kit. Gene expression levels were assessed by real‐time PCR. Predesigned SNP genotyping assays were obtained from ThermoFisher. The appropriate internal controls to be used for normalization were selected using NormFinder. Statistical analysis was performed using SPSS. False discovery rate (FDR) correction for multiple testing was used to rule out false positive results.

Results: In light of the results of the NormFinder analysis, normalization was performed with GAPDH for ZDHHC19 and RNU6 for micro RNAs. A case–control study showed a significant association between ZDHHC19 gene expression levels and sepsis. We found a connection between the expression of the gene and some clinical variables (neutrophils %, lymphocytes, C reactive protein, procalcitonin). No association could be observed between the phenotypic data and the polymorphisms in the ZDHHC19 gene.

Conclusion: Our results suggest that the ZDHHC19 enzyme contributes to the molecular background of sepsis, presumably modulating the function of neutrophil granulocytes. However, further studies are necessitated to prove the causal relationship of the demonstrated correlations and to clarify the exact cellular role of ZDHHC19 in sepsis.

Funding: This research was funded by the National Research, Development, and Innovation Office (grant number: K-131680)