Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles?
Decompensated cirrhosis is the most common cause of ascites due to hemodynamic and renal alteration by continuous fluid leakage from the hepatic sinusoids and splanchnic capillaries into the interstitial space. Then, fluid leakage exceeds lymphatic return, leading to progressive fluid accumulation d...
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MDPI AG
2023-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/9/2405 |
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| author | Isabel Legaz Raquel Morales José Miguel Bolarín Aurelia Collados-Ros José Antonio Pons Manuel Muro |
| author_facet | Isabel Legaz Raquel Morales José Miguel Bolarín Aurelia Collados-Ros José Antonio Pons Manuel Muro |
| author_sort | Isabel Legaz |
| collection | DOAJ |
| description | Decompensated cirrhosis is the most common cause of ascites due to hemodynamic and renal alteration by continuous fluid leakage from the hepatic sinusoids and splanchnic capillaries into the interstitial space. Then, fluid leakage exceeds lymphatic return, leading to progressive fluid accumulation directly into the peritoneal cavity. Alcohol consumption is one of the main risks of developing alcoholic cirrhosis (AC), but not all AC patients develop ascites. Avoiding the development of ascites is crucial, given that it deteriorates prognosis and increases the patient mortality patient. The innate immune system plays a crucial role in cirrhosis through natural killer cells, which are abundant in the liver. The aim of this study was to analyze the KIR/HLA-C genetic profile in AC patients with and without ascites to understand this pathology and find predictive clinical susceptibility biomarkers that can help to establish risks and prevent the development of ascites in AC patients. A total of 281 AC patients with and without ascites were analyzed and compared with 319 healthy controls. Genomic DNA was extracted from peripheral blood in all groups. A PCR-SSO assay was performed for KIR/HLA genotyping analysis. A total of 16 activating and inhibitor KIR genes and their corresponding known ligands, epitopes of HLA-C, and their genotypes were analyzed. According to our analysis, C1 epitopes were statistically significantly decreased in AC patients with and without ascites. When comparing AC patients with ascites and healthy controls, a significant decrease in C1 epitope frequency was also observed. A statistically significant decrease was also found when comparing the C1C2 genotype in AC patients without ascites with controls. In conclusion, the absence of KIR2DL2 and KIR3DL1 genes may be a predisposing factor for the development of ascites in AC patients. The KIR2DS2/KIR2DL2 may could be involved in grade I ascites development, and the presence of the C1+ epitope and the homozygous C2C2 genotype may be protective genetic factors against ascites development in AC patients. |
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| language | English |
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| publishDate | 2023-08-01 |
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| spelling | doaj.art-2c32dd4b9a8947669c63271e3eea7d622023-11-19T09:40:50ZengMDPI AGBiomedicines2227-90592023-08-01119240510.3390/biomedicines11092405Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles?Isabel Legaz0Raquel Morales1José Miguel Bolarín2Aurelia Collados-Ros3José Antonio Pons4Manuel Muro5Department of Legal and Forensic Medicine, Biomedical Research Institute of Murcia (IMIB), Regional Campus of International Excellence “Campus Mare Nostrum”, Faculty of Medicine, University of Murcia (UMU), 30100 Murcia, SpainDepartment of Legal and Forensic Medicine, Biomedical Research Institute of Murcia (IMIB), Regional Campus of International Excellence “Campus Mare Nostrum”, Faculty of Medicine, University of Murcia (UMU), 30100 Murcia, SpainDepartment of Legal and Forensic Medicine, Biomedical Research Institute of Murcia (IMIB), Regional Campus of International Excellence “Campus Mare Nostrum”, Faculty of Medicine, University of Murcia (UMU), 30100 Murcia, SpainDepartment of Legal and Forensic Medicine, Biomedical Research Institute of Murcia (IMIB), Regional Campus of International Excellence “Campus Mare Nostrum”, Faculty of Medicine, University of Murcia (UMU), 30100 Murcia, SpainDepartment of Hepatology, Liver Transplantation Unit Hospital Clinic Universitario, Virgen de la Arrixaca, IMIB-Arrixaca, 30120 Murcia, SpainImmunology Service, University Clinical Hospital “Virgen de la Arrixaca”—IMIB, 30120 Murcia, SpainDecompensated cirrhosis is the most common cause of ascites due to hemodynamic and renal alteration by continuous fluid leakage from the hepatic sinusoids and splanchnic capillaries into the interstitial space. Then, fluid leakage exceeds lymphatic return, leading to progressive fluid accumulation directly into the peritoneal cavity. Alcohol consumption is one of the main risks of developing alcoholic cirrhosis (AC), but not all AC patients develop ascites. Avoiding the development of ascites is crucial, given that it deteriorates prognosis and increases the patient mortality patient. The innate immune system plays a crucial role in cirrhosis through natural killer cells, which are abundant in the liver. The aim of this study was to analyze the KIR/HLA-C genetic profile in AC patients with and without ascites to understand this pathology and find predictive clinical susceptibility biomarkers that can help to establish risks and prevent the development of ascites in AC patients. A total of 281 AC patients with and without ascites were analyzed and compared with 319 healthy controls. Genomic DNA was extracted from peripheral blood in all groups. A PCR-SSO assay was performed for KIR/HLA genotyping analysis. A total of 16 activating and inhibitor KIR genes and their corresponding known ligands, epitopes of HLA-C, and their genotypes were analyzed. According to our analysis, C1 epitopes were statistically significantly decreased in AC patients with and without ascites. When comparing AC patients with ascites and healthy controls, a significant decrease in C1 epitope frequency was also observed. A statistically significant decrease was also found when comparing the C1C2 genotype in AC patients without ascites with controls. In conclusion, the absence of KIR2DL2 and KIR3DL1 genes may be a predisposing factor for the development of ascites in AC patients. The KIR2DS2/KIR2DL2 may could be involved in grade I ascites development, and the presence of the C1+ epitope and the homozygous C2C2 genotype may be protective genetic factors against ascites development in AC patients.https://www.mdpi.com/2227-9059/11/9/2405alcoholic cirrhosisasciteshuman clinical toxicologyliver transplantKIR/HLA-C genes |
| spellingShingle | Isabel Legaz Raquel Morales José Miguel Bolarín Aurelia Collados-Ros José Antonio Pons Manuel Muro Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles? Biomedicines alcoholic cirrhosis ascites human clinical toxicology liver transplant KIR/HLA-C genes |
| title | Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles? |
| title_full | Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles? |
| title_fullStr | Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles? |
| title_full_unstemmed | Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles? |
| title_short | Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles? |
| title_sort | is the development of ascites in alcoholic liver patients influenced by specific kir hla gene profiles |
| topic | alcoholic cirrhosis ascites human clinical toxicology liver transplant KIR/HLA-C genes |
| url | https://www.mdpi.com/2227-9059/11/9/2405 |
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