CETP genetic variant rs1800777 (allele A) is associated with abnormally low HDL-C levels and increased risk of AKI during sepsis
| Autor: | HyeJin Julia Kong, Mark Trinder, Tadanaga Shimada, John H. Boyd, Keith R. Walley, Kelly R. Genga, Xuan Li, Gordon A. Francis, Alex K. K. Leung, James A. Russell, Liam R. Brunham |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty lcsh:Medicine 030204 cardiovascular system & hematology Gastroenterology Polymorphism Single Nucleotide Article Sepsis Cohort Studies 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Cholesterylester transfer protein Genetic variation Genotype Medicine Humans Allele lcsh:Science Alleles Aged Multidisciplinary biology business.industry Cholesterol Septic shock lcsh:R Cholesterol HDL Acute kidney injury Acute Kidney Injury Middle Aged medicine.disease 3. Good health Cholesterol Ester Transfer Proteins 030104 developmental biology chemistry biology.protein lcsh:Q lipids (amino acids peptides and proteins) Female business |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-8 (2018) |
| ISSN: | 2045-2322 |
| Popis: | High-density cholesterol (HDL-C) levels are influenced by genetic variation in several genes. Low levels of HDL-C have been associated with increased risk of acute kidney injury (AKI). We investigated whether genetic polymorphisms in ten genes known to regulate HDL-C levels are associated with both HDL-C levels and AKI development during sepsis. Two cohorts were retrospectively analyzed: Derivation Cohort (202 patients with sepsis enrolled at the Emergency Department from 2011 to 2014 in Vancouver, Canada); Validation Cohort (604 septic shock patients enrolled into the Vasopressin in Septic Shock Trial (VASST)). Associations between HDL-related genetic polymorphisms and both HDL-C levels, and risk for clinically significant sepsis-associated AKI (AKI KDIGO stages 2 and 3) were evaluated. In the Derivation Cohort, one genetic variant in the Cholesteryl Ester Transfer Protein (CETP) gene, rs1800777 (allele A), was strongly associated with lower HDL-C levels (17.4 mg/dL vs. 32.9 mg/dL, P = 0.002), greater CETP mass (3.43 µg/mL vs. 1.32 µg/mL, P = 0.034), and increased risk of clinically significant sepsis-associated AKI (OR: 8.28, p = 0.013). Moreover, the same allele was a predictor of sepsis-associated AKI in the Validation Cohort (OR: 2.38, p = 0.020). Our findings suggest that CETP modulates HDL-C levels in sepsis. CETP genotype may identify patients at high-risk of sepsis-associated AKI. |
| Databáze: | OpenAIRE |
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