| Endothelial nitric oxide synthase gene variation associated with chronic kidney disease after liver transplant. | |
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MedLine Citation:
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PMID: 20810793 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT). PATIENTS AND METHODS: This study consists of a cohort of adult (> or =18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, > or =40 mL/min per 1.73 m(2) during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m(2) after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables. RESULTS: The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables). CONCLUSION: Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD. |
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Authors:
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Kiran Bambha; W Ray Kim; Charles B Rosen; Rachel A Pedersen; Cynthia Rys; Christopher P Kolbert; Julie M Cunningham; Terry M Therneau |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Mayo Clinic proceedings. Mayo Clinic Volume: 85 ISSN: 1942-5546 ISO Abbreviation: Mayo Clin. Proc. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-02 Completed Date: 2010-09-27 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 0405543 Medline TA: Mayo Clin Proc Country: United States |
Other Details:
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Languages: eng Pagination: 814-20 Citation Subset: AIM; IM |
Affiliation:
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Division of Gastroenterology and Hepatology, University of Colorado Health Sciences Center, Denver, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Female Genetic Association Studies* Genotype Glomerular Filtration Rate Homozygote Humans Kaplan-Meier Estimate Kidney Failure, Chronic / etiology, genetics* Liver Transplantation / adverse effects* Male Middle Aged Nitric Oxide Synthase Type III / genetics* Polymorphism, Single Nucleotide / genetics* Proportional Hazards Models |
| Grant Support | |
ID/Acronym/Agency:
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AT-004174/AT/NCCAM NIH HHS; DK-34238/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type III |
| Comments/Corrections | |
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