Dataset Information

Genetic determinants of pancreatitis: relevance in severe hypertriglyceridemia.

ABSTRACT:

Purpose of review

Not all patients with severe hypertriglyceridemia develop acute pancreatitis. We surveyed recent literature on inter-individual genetic variation in susceptibility to pancreatitis.

Recent findings

Genetic determinants of pancreatitis include: rare Mendelian disorders caused by highly penetrant pathogenic variants in genes involved in trypsinogen activation; uncommon susceptibility variants in genes involved in trypsinogen activation, protein misfolding as well as calcium metabolism and cystic fibrosis, that have variable penetrance and show a range of odds ratios for pancreatitis; and common polymorphisms in many of the same genes that have only a small effect on risk. The role of these genetic variants in modulating pancreatitis risk in hypertriglyceridemia is unclear. However, among genetic determinants of plasma triglycerides, those predisposing to more severe hypertriglyceridemia associated with chylomicronemia appear to have higher pancreatitis risk.

Summary

Currently, among patients with severe hypertriglyceridemia, the most consistent predictor of pancreatitis risk is the triglyceride level. Furthermore, pancreatitis risk appears to be modulated by a higher genetic burden of factors associated with greater magnitude of triglyceride elevation. The role of common and rare genetic determinants of pancreatitis itself in this metabolic context is unclear.

SUBMITTER: Hang SMT

PROVIDER: S-EPMC10069755 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Genetic determinants of pancreatitis: relevance in severe hypertriglyceridemia.

Hang Shyann M T SMT Hegele Robert A RA Berberich Amanda J AJ

Current opinion in lipidology 20230201 2

<h4>Purpose of review</h4>Not all patients with severe hypertriglyceridemia develop acute pancreatitis. We surveyed recent literature on inter-individual genetic variation in susceptibility to pancreatitis.<h4>Recent findings</h4>Genetic determinants of pancreatitis include: rare Mendelian disorders caused by highly penetrant pathogenic variants in genes involved in trypsinogen activation; uncommon susceptibility variants in genes involved in trypsinogen activation, protein misfolding as well as ...[more]

PMID: 36752614

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Project description:The incidence of hypertriglyceridemia induced acute pancreatitis (HTAP) continues to rise in China. It has systemic complications and high mortality, making the early assessment of the severity of this disease even more important. Circulating microRNAs (miRNAs) could be novel, non-invasive biomarkers for disease progression judgment. This study aimed to identify the potential role of serum miRNAs as novel biomarkers of HTAP progression. HTAP patients were divided into two groups: moderately severe (HTMSAP) and severe (HTSAP), healthy people were used as control group. The serum miRNA expression profiles of these three groups were determined by microarray and verified by qRT-PCR. The functions and pathways of the targeted genes of deregulated miRNAs were predicted, using bioinformatics analysis; miRNA-mRNA network was generated. Moreover, the correlation between miR-181a-5p and pancreatitis metabolism related substances were studied and the serum concentration of inflammatory cytokines and miRNAs at different time points during the MSAP and SAP were investigated, respectively. Finally, the receiver operating characteristic (ROC) curve of miRNAs was studied. Significant changes in the serum concentration of the following miRNAs of HTAP patients (P<0.05) were discovered: miR24-3p, 361-5p, 1246, and 222-3p (constantly upregulated), and 181a-5p (constantly downregulated) (P<0.05). Bioinformatics analysis predicted that 13 GOs and 36 pathways regulated by overlap miRNAs were involved in glucose, fat, calcium (Ca++), and insulin metabolism (P<0.001). miRNA-mRNA network revealed that the overlap miRNAs targeted genes participating in pancreas metabolism and miR-181a-5p, the only downregulated miRNA, had good negative correlation with triglyceride (TG), total cholesterol (TC), and fast blood glucose (FBG), but a positive correlation with Ca++. When compared with inflammatory cytokines, the changes of all five overlap miRNAs were more stable. It was found that when used for evaluating the progression of HTAP, miRNAs showed good AUC. These data suggested that serum miRNAs have the potential to be excellent HTAP biomarkers.

Dataset Information

Genetic determinants of pancreatitis: relevance in severe hypertriglyceridemia.

Purpose of review

Recent findings

Summary

Publications

Genetic determinants of pancreatitis: relevance in severe hypertriglyceridemia.

Similar Datasets

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