The common truncation variant in pancreatic lipase related protein 2 (PNLIPRP2) is expressed poorly and does not alter risk for chronic pancreatitis

Németh, Balázs Csaba; Pesei, Zsofia Gabriella; Hegyi, E; Szücs, Ákos; Szentesi, Andrea; Hegyi, Péter; Lowe, Mark E.; Sahin–Tóth, Miklós

doi:10.1371/journal.pone.0206869

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…3c , the PNLIPRP2 programmed cell death 6 (PDCD6), a lipase, which contributes to milk fat hydrolysis 20 , is shown with the genetic variants associated with the plasma levels found in conjunction with the location of the protein-coding gene (cytoband 10q25.3 on the genome). The most significant association was found for variant rs4751995, which is a common truncation variant in PNLIPRP2 and was first described in 2003 as W357X in European cohort 21 . The longitudinal analysis during the three visits for the 76 subjects in the wellness study demonstrates that the protein levels are high for both the homozygote and heterozygotes for the variant, and the differences were stable during the 2-year study period.…”

Section: Resultsmentioning

confidence: 96%

Next generation plasma proteome profiling to monitor health and disease

et al. 2021

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The need for precision medicine approaches to monitor health and disease makes it important to develop sensitive and accurate assays for proteome profiles in blood. Here, we describe an approach for plasma profiling based on proximity extension assay combined with next generation sequencing. First, we analyze the variability of plasma profiles between and within healthy individuals in a longitudinal wellness study, including the influence of genetic variations on plasma levels. Second, we follow patients newly diagnosed with type 2 diabetes before and during therapeutic intervention using plasma proteome profiling. The studies show that healthy individuals have a unique and stable proteome profile and indicate that a panel of proteins could potentially be used for early diagnosis of diabetes, including stratification of patients with regards to response to metformin treatment. Although validation in larger cohorts is needed, the analysis demonstrates the usefulness of comprehensive plasma profiling for precision medicine efforts.

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Section: Resultsmentioning

confidence: 96%

Next generation plasma proteome profiling to monitor health and disease

et al. 2021

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“…Figure 11D), and partial protection from GTLinduced injury in acini from the PNLIP-KO mice ( Figure 5, F and G). However, PNLIPRP2's clinical relevance is likely to be low because about 50% of Europeans are heterozygous and 20% homozygous for a common PNLIPRP2 truncation variant that results in nonsense-mediated decay, thus inhibiting expression of PNLIPRP2 at the mRNA level (70). Because CEL cannot effectively hydrolyze triglycerides with fatty acids of greater than 16 carbon chains (38,39) and requires bile acid concentrations much higher than in pancreatic necrosis collections (40), it is unlikely to play a major role in fat necrosis.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation

Oliveira¹,

Khatua²,

Noel³

et al. 2020

Journal of Clinical Investigation

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“…We also realized that four putative T2DM-associated DEGs have been reported to be involved in ER stress (48)(49)(50)(51): PNLIPRP2, SDF2L1, ALOX15, and RNF186. The RING finger E3 ligase RNF186 evidently regulates ER stress-mediated apoptosis through interaction with BNip1 in HeLa cells (36,(51)(52)(53)(54).…”

Section: Discussionmentioning

confidence: 82%

Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats

et al. 2020

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Around 9% of the adult population in the world (463 million) suffer from diabetes mellitus. Most of them (~90%) belong to type 2 diabetes mellitus (T2DM), which is a common chronic metabolic disorder, and the number of cases has been reported to increase each year. Zucker diabetic fatty (ZDF) rat provides a successful animal model to study the pathogenesis of T2DM. Although previous hepatic transcriptome studies revealed some novel genes associated with the occurrence and development of T2DM, there still lacks the comprehensive transcriptomic analysis for the liver tissues of ZDF rats. We performed comparative transcriptome analyses between the liver tissues of ZDF rats and healthy ZCL rats and also evaluated several clinical indices. We could identify 214 and 104 differentially expressed genes (DEGs) and lncRNAs in ZDF rats, respectively. Pathway and biofunction analyses showed a synergistic effect between mRNAs and lncRNAs. By comprehensively analyzing transcriptomic data and clinical indices, we detected some typical features of T2DM in ZDF rats, such as upregulated metabolism (significant increased lipid absorption/transport/utilization, gluconeogenesis, and protein hydrolysis), increased inflammation, liver injury and increased endoplasmic reticulum (ER) stress. In addition, of the 214 DEGs, 114 were known and 100 were putative T2DM-related genes, most of which have been associated with substance metabolism (particularly degradation), inflammation, liver injury and ER stress biofunctions. Our study provides an important reference and improves understanding of molecular pathogenesis of obesity-associated T2DM. Our data can also be used to identify potential diagnostic markers and therapeutic targets, which should strengthen the prevention and treatment of T2DM.

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The common truncation variant in pancreatic lipase related protein 2 (PNLIPRP2) is expressed poorly and does not alter risk for chronic pancreatitis

Cited by 7 publications

References 27 publications

Next generation plasma proteome profiling to monitor health and disease

Next generation plasma proteome profiling to monitor health and disease

Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation

Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats

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