Abstract 18879: Nicotinamide Phosphoribosyltransferase as a Potential New Genetic Biomarker for Stroke
Introduction: We reported that Nicotinamide Phosphoribosyltransferase (NAMPT, also called PBEF) displays a protective role in acute ischemic stroke in both mouse and neuronal cell models. We had also identified that NAMPT SNPs in the human NAMPT gene promoter were associated with acute respiratory distress syndrome. This study aimed to determine whether NAMPT SNPs are associated with stroke by genetic association and reporter gene assays.
Methods: Four NAMPT SNPs (G-1535A,A-1001C, C-948A, T-423C) were genotyped using the Taqman Assay on stroke patient population from the Coriell biorepository (n = 376), consisting of Caucasian and African American patients, and compared to healthy controls (n = 625) from the 1000 Human Genomes Project. Their haplotypes and diplotypes were analyzed using HPlus software (FHCRC, Seattle, WA). Stratified analyses included: race, gender, hypertension, diabetes, family history of cerebrovascular disease, atrial fibrillation, and history of smoking. Significant NAMPT promoter SNP haplotypes and diplotypes were identified and are being tested in luciferase reporter gene assays in SH-SY5Y neuroblastoma cells.
Results: In this study, within the African American population carriers of the ‘protective haplotype’ of GACT had a significantly lower risk of stroke (OR= 0.59, 95% CI, 0.35-0.996, p<0.05). Carriers of the ‘susceptible haplotype’ of AACT had a 2.16 fold increased risk of stroke (95% CI, 1.28-3.63, p<0.01) in the African American population. In the combined Caucasian and African American population we found several NAMPT haplotypes and diplotypes associated with stroke risk factors such as diabetes, family history, smoking history and atrial fibrillation. Notably, carriers of the ‘susceptible haplotype’ GACC (OR= 3.435, 95% CI, 1.529-7.717, p<0.01) were found in the diabetes positive subpopulation of stroke patients. Reporter gene assays to identify the affect these haplotypes and diplotypes have on transcription efficiency are currently in progress.
Conclusions: These results suggest that NAMPT is a potential new predictive genetic biomarker for human stroke though the replication of this observation in larger patient populations and the further exploration of underpinning mechanisms are warranted.
Author Disclosures: S.M. Riordan: None. D. Cherenova: None. S. Chaudhary: None. I. Sokolovsky: None. D. Heruth: None. D. Grigoryev: None. L.Q. Zhang: None. S.Q. Ye: None.
- © 2014 by American Heart Association, Inc.