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Association Between a Sirtuin 5 SNP (rs SIRT5 SNP, rs9382222) and Three Functional Markers of Brain Health

Velazquez, Enrique Israel (2011) Association Between a Sirtuin 5 SNP (rs SIRT5 SNP, rs9382222) and Three Functional Markers of Brain Health. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Velazquez, Enrique Israeleiv2@pitt.eduEIV2
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLaPorte, Ronald E.ronaldlaporte@gmail.com
Committee MemberKammerer, Candace M.cmk3@pitt.eduCMK3
Committee MemberRosano, Caterinarosanoc@edc.pitt.eduCAR2350
Committee MemberSibille, Etienne L. sibilleel@upmc.edu
Date: 23 September 2011
Date Type: Completion
Defense Date: 22 July 2011
Approval Date: 23 September 2011
Submission Date: 24 July 2011
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: BRAIN GENETICS; BRAIN HEALTH; OLDER POPULATION; PUBLIC HEALTH GENETICS; rs9382222; SIRTUIN 5 SNP
Other ID: http://etd.library.pitt.edu/ETD/available/etd-07242011-120604/, etd-07242011-120604
Date Deposited: 10 Nov 2011 19:53
Last Modified: 15 Nov 2016 13:46
URI: http://d-scholarship.pitt.edu/id/eprint/8575

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