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Associations between single nucleotide polymorphisms in the FAS pathway and acute kidney injury.

ABSTRACT: INTRODUCTION:To determine whether single nucleotide polymorphisms (SNPs) in FAS and related genes are associated with acute kidney injury (AKI) in patients with acute respiratory distress syndrome (ARDS). METHODS:We studied 401 (Caucasian N = 310 and African-American N = 91) patients aged ? 13 years with ALI who enrolled in the Fluid and Catheter Treatment Trial (FACTT) between 2000 and 2005 from 20 North American centers. We genotyped 367 SNPs in 45 genes of the Fas/Fas ligand pathway to identify associations between SNPs in Fas pathway genes and the development of AKI by day 2 after enrollment in FACTT, adapting Acute Kidney Injury Network (AKIN) criteria. Written informed consent was obtained from participants or legally authorized surrogates in the original FACTT study and available to use for secondary analysis. RESULTS:In Caucasian patients, we identified associations between two SNPs and the incidence of AKI (stage 1 and above): rs1050851 and rs2233417; both are found within the gene for nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA). For rs1050851 and rs2233417, the odds ratios (ORs) were 2.34 (95 % confidence interval (CI) = 1.58-3.46, p = 1.06 × 10(-5), FDR = 0.003) and 2.46 (CI = 1.61-3.76, p = 1.81 × 10(-5), FDR = 0.003) for each minor allele, respectively. The associations were stronger still for AKIN stage 2-3 with respective ORs 4.00 (CI = 2.10-7.62, p = 1.05 × 10(-5), FDR = 0.003) and 4.03 (CI = 2.09-7.77, p = 1.88 × 10(-5), FDR = 0.003) for each minor allele homozygote. We observed no significant association between these SNPs and AKI in the smaller subset of African Americans. CONCLUSION:In Caucasian patients with ALI, the presence of minor alleles in two SNPs in NFKBIA was strongly associated with the development of AKI. TRIAL REGISTRATION:NCT00281268 . Registered 20/01/2006.

SUBMITTER: Bhatraju P

PROVIDER: S-EPMC4610046 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Associations between single nucleotide polymorphisms in the FAS pathway and acute kidney injury.

Bhatraju Pavan P Hsu Christine C Mukherjee Paramita P Glavan Bradford J BJ Burt Amber A Mikacenic Carmen C Himmelfarb Jonathan J Wurfel Mark M

Critical care (London, England) 20151019

<h4>Introduction</h4>To determine whether single nucleotide polymorphisms (SNPs) in FAS and related genes are associated with acute kidney injury (AKI) in patients with acute respiratory distress syndrome (ARDS).<h4>Methods</h4>We studied 401 (Caucasian N = 310 and African-American N = 91) patients aged ≥ 13 years with ALI who enrolled in the Fluid and Catheter Treatment Trial (FACTT) between 2000 and 2005 from 20 North American centers. We genotyped 367 SNPs in 45 genes of the Fas/Fas ligand pa ...[more]

PMID: 26477820

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Project description:BACKGROUND:FAS cell surface death receptor (FAS) gene has 2 common single nucleotide polymorphisms (SNPs) in its promoter, FAS-1377G?>?A (rs2234767) and FAS-670A?>?G (rs1800682). Several studies have investigated the role of these 2 polymorphisms in etiology of breast cancer in Asian population while the outcomes are inconsistent. To derive a more precise assessment of the association between breast cancer susceptibility with FAS gene promoter SNPs, a meta-analysis of published studies was performed. MATERIAL AND METHODS:We systematically searched PubMed, Embase, Web of Science, and the Chinese biomedical database (CBM) for papers published until November 1, 2018. Odds ratio (OR) with 95% confidential interval (95%CI) was conducted to evaluate the associations. Statistical analysis was conducted using Stata13.0 software. A total of 8 studies covering 2564 cases and 2633 controls were included. RESULTS:The integrated results suggest the following: For the FAS-1377G/A polymorphism, we only found significant associations for allele G vs allele A (OR?=?1.100, 95%CI?=?1.004-1.206, P?=?.040). After stratification by ethnicity, a significant association was observed only for the AA+GA vs GG genotype in East Asian populations (OR?=?1.177, 95% CI?=?1.010-1.371, P?=?.037). The association was not found in West Asian populations. For the FAS -670A/G polymorphism, no association with cancer risk was found in any comparison model. Sensitivity analysis suggests that the meta-analysis results obtained after excluding any single study were similar to the original ones, suggesting that the meta-analysis results were not significantly affected by any single study. CONCLUSION:These results indicated that FAS-1377G/A polymorphism may contribute to the increased breast cancer susceptibility and could be a promising target for cancer risk prediction. Further studies are needed to determine if the FAS gene confers a risk of breast cancer in other ethnic groups, such as Africans and Latin Americans.

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Associations between single nucleotide polymorphisms in the FAS pathway and acute kidney injury.

Publications

Associations between single nucleotide polymorphisms in the FAS pathway and acute kidney injury.

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