High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease
<i>Background and Objectives</i>: Patients with GG rs738409 patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype (148M variant) have greater risk to develop end-stage liver disease and its associated clinical complications, including hepatocellular carcinoma (HCC). We...
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2025-07-01
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| Online Access: | https://www.mdpi.com/1648-9144/61/7/1293 |
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| author | Ivan Budimir Bekan Dino Šisl Alan Šućur Ana Bainrauch Valerija Bralić Lang Pavao Planinić Nataša Kovačić Danka Grčević Anna Mrzljak Tomislav Kelava |
| author_facet | Ivan Budimir Bekan Dino Šisl Alan Šućur Ana Bainrauch Valerija Bralić Lang Pavao Planinić Nataša Kovačić Danka Grčević Anna Mrzljak Tomislav Kelava |
| author_sort | Ivan Budimir Bekan |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: Patients with GG rs738409 patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype (148M variant) have greater risk to develop end-stage liver disease and its associated clinical complications, including hepatocellular carcinoma (HCC). We aimed to analyze the association between the PNPLA3 genotype and augmented inflammatory response in transplant candidates with end-stage alcoholic liver disease (ALD). <i>Materials and Methods</i>: Concentrations of 13 cytokines were measured in 106 end-stage ALD patients without HCC (40 with CC, 40 with CG, and 26 with GG genotype), 35 end-stage ALD patients with HCC, and 19 control patients by cytometric bead array. <i>Results</i>: We found significantly higher concentrations of IL-1, IFN-α, IFN-γ, TNF-α, IL-6, CXCL8, IL-10, IL-12, IL-32, and IL-33 in patients with ALD compared to controls, while the concentration of CCL2 was significantly lower. No differences were observed in the concentration of IL-17 and IL-18. ALD patients with and without HCC had similar cytokine concentrations (<i>p</i> > 0.05 for all comparisons). End-stage ALD patients without HCC of the GG genotype had significantly higher CCL2 concentrations (212.6 [135.9–264.9] pg/mL) compared to end-stage ALD patients without HCC carrying the CC/CG genotypes (141.3 [104.1–201.6] pg/mL, <i>p</i> = 0.002, Mann–Whitney). No significant differences across the genotypes were found for the remaining measured cytokines (<i>p</i> > 0.05). GG carriers also had significantly higher levels of AST and ALT, and lower platelet counts. <i>Conclusions</i>: End-stage ALD patients without HCC who carry the PNPLA3 GG genotype have relatively higher CCL2 levels compared to those with the CC or CG genotypes. Relatively elevated CCL2 concentrations in GG patients might contribute to their increased risk of developing clinical complications compared to CC/CG patients. |
| format | Article |
| id | doaj-art-64700bc02c334a4bb7a137e323b88d81 |
| institution | DOAJ |
| issn | 1010-660X 1648-9144 |
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| publishDate | 2025-07-01 |
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| spelling | doaj-art-64700bc02c334a4bb7a137e323b88d812025-08-20T03:07:55ZengMDPI AGMedicina1010-660X1648-91442025-07-01617129310.3390/medicina61071293High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver DiseaseIvan Budimir Bekan0Dino Šisl1Alan Šućur2Ana Bainrauch3Valerija Bralić Lang4Pavao Planinić5Nataša Kovačić6Danka Grčević7Anna Mrzljak8Tomislav Kelava9Department of Surgery, Merkur University Hospital, 10000 Zagreb, CroatiaLaboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, 10000 Zagreb, CroatiaLaboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Internal Medicine, Merkur University Hospital, 10000 Zagreb, CroatiaPrivate Family Physician Office Zagreb, 10000 Zagreb, CroatiaDepartment of Physiology, School of Medicine, University of Mostar, 88000 Mostar, Bosnia and HerzegovinaLaboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, 10000 Zagreb, CroatiaLaboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, 10000 Zagreb, CroatiaSchool of Medicine, University of Zagreb, 10000 Zagreb, CroatiaLaboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, 10000 Zagreb, Croatia<i>Background and Objectives</i>: Patients with GG rs738409 patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype (148M variant) have greater risk to develop end-stage liver disease and its associated clinical complications, including hepatocellular carcinoma (HCC). We aimed to analyze the association between the PNPLA3 genotype and augmented inflammatory response in transplant candidates with end-stage alcoholic liver disease (ALD). <i>Materials and Methods</i>: Concentrations of 13 cytokines were measured in 106 end-stage ALD patients without HCC (40 with CC, 40 with CG, and 26 with GG genotype), 35 end-stage ALD patients with HCC, and 19 control patients by cytometric bead array. <i>Results</i>: We found significantly higher concentrations of IL-1, IFN-α, IFN-γ, TNF-α, IL-6, CXCL8, IL-10, IL-12, IL-32, and IL-33 in patients with ALD compared to controls, while the concentration of CCL2 was significantly lower. No differences were observed in the concentration of IL-17 and IL-18. ALD patients with and without HCC had similar cytokine concentrations (<i>p</i> > 0.05 for all comparisons). End-stage ALD patients without HCC of the GG genotype had significantly higher CCL2 concentrations (212.6 [135.9–264.9] pg/mL) compared to end-stage ALD patients without HCC carrying the CC/CG genotypes (141.3 [104.1–201.6] pg/mL, <i>p</i> = 0.002, Mann–Whitney). No significant differences across the genotypes were found for the remaining measured cytokines (<i>p</i> > 0.05). GG carriers also had significantly higher levels of AST and ALT, and lower platelet counts. <i>Conclusions</i>: End-stage ALD patients without HCC who carry the PNPLA3 GG genotype have relatively higher CCL2 levels compared to those with the CC or CG genotypes. Relatively elevated CCL2 concentrations in GG patients might contribute to their increased risk of developing clinical complications compared to CC/CG patients.https://www.mdpi.com/1648-9144/61/7/1293cytokinealcoholic liver diseasesingle nucleotide polymorphismliver transplantationPNPLA3 148Mchemokine (C-C motif) ligand 2 |
| spellingShingle | Ivan Budimir Bekan Dino Šisl Alan Šućur Ana Bainrauch Valerija Bralić Lang Pavao Planinić Nataša Kovačić Danka Grčević Anna Mrzljak Tomislav Kelava High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease Medicina cytokine alcoholic liver disease single nucleotide polymorphism liver transplantation PNPLA3 148M chemokine (C-C motif) ligand 2 |
| title | High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease |
| title_full | High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease |
| title_fullStr | High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease |
| title_full_unstemmed | High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease |
| title_short | High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease |
| title_sort | high risk pnpla3 rs738409 genotype is associated with higher concentrations of ccl2 in liver transplant candidates with alcoholic end stage liver disease |
| topic | cytokine alcoholic liver disease single nucleotide polymorphism liver transplantation PNPLA3 148M chemokine (C-C motif) ligand 2 |
| url | https://www.mdpi.com/1648-9144/61/7/1293 |
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