This study is based on an a priori hypothesis for a particular SNP in the SIRT5 gene (rs9382222; C¨T) for which we have evidence that the common C-allele is associated with an older biological age of the brain. Digit Symbol Substitution Test (DSST), 20 meters timed-walk (Gait Test) and Epidemiological Studies Depression Scale (CES-D) are functional markers of brain health and applicable tests to measure cognitive function, motor function and depressed mood. HYPOTHESIS: At baseline, subjects carrying the common C/C risk genotype at the SIRT5 SNP will display poorer function on cognitive function tests (lower DSST score) and motor function tests (longer time to walk 20 meters), and have increased self-reported symptoms of a depressed mood (higher CES-D score), as compared to all other subjects. METHODS: The linear model type, one-way analysis of covariance (ANCOVA), was fitted using SAS GLM procedure to test for between-group differences in functional outcomes. Concordance in SNP effects were investigated for the three interrelated functional markers in subjects carrying the specific genotype (C/C, C/T, T/T). RESULTS: We detected a borderline significant association between DSST and SNP in the black population (p=0.051, mean diff.=-0.05, SD=0.95) with C/C subjects displaying lower DSST scores vs. C/T (almost 2 units lower than heterozygotes). There is a trend for an association between CES-D and SNP in the white population (p=0.08, mean diff.=-1.85, SD=0.03) with the C/C risk group reporting higher depression-like symptoms vs. C/T. Gait Test were no statistical significant associated to the SNP. CONCLUSIONS: The C/C previously linked with older biological brain age was associated with (1) lower DSST scores in the black population and (2) displayed trend-level higher CES-D depressive-like scores in the white population, hence suggesting the SIRT5 C/C genotype as a probable risk factor for both biological brain age and related functional outcomes. PUBLIC HEALTH SIGNIFICANCE: Emotional and cognitive fitness is rapidly becoming a major determinant to the quality of life during old age. Study the genetic component of the brain aging as this SNP would help to 1) identify people at risk, and 2) address public health programs to achieve a successful aging.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-07242011-120604 |
| Date | 23 September 2011 |
| Creators | Velazquez, Enrique Israel |
| Contributors | Etienne L. Sibille, Ph.D., Ronald E. LaPorte, Ph.D., Candace M. Kammerer, Ph.D., Caterina Rosano, M.D., M.P.H. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-07242011-120604/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.1208 seconds