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The Catechol-O-Methyltransferase Genotype, Frailty and Gait speed: The Cardiovascular Health Study

Mance, Shannon (2020) The Catechol-O-Methyltransferase Genotype, Frailty and Gait speed: The Cardiovascular Health Study. Master Essay, University of Pittsburgh.

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Abstract

Objective: To examine whether the association between dopamine-related genotype and gait speed differs according to frailty status or race.
Design: Cross-sectional population-based study (Cardiovascular Health Study)
Setting: Multi-center study, 4 US sites.
Participants: Volunteer community-dwelling adults aged 65 and older, without evidence of Parkinson’s Disease (N= 3,744, 71 years, 82% white, 39% male).
Measurements: Gait speed (usual pace, m/sec), physical frailty (Fried definition), and genetic polymorphism of Catechol-O-methyltransferase (COMT, rs4680), an enzyme regulating tonic brain dopamine levels, were assessed. Interaction of COMT by frailty and by race predicting gait speed were tested, and, if significant, analyses were stratified. Multivariable regression models of COMT predicting gait speed were adjusted for demographics and locomotor risk factors. Sensitivity analyses were repeated stratified by clinical cut-offs of gait speed (0.6 and 1.0m/sec) instead of frailty status.
Results: Compared to Met/Met (higher dopaminergic signaling), the Val/Val group (lower dopaminergic signaling) walked marginally more slowly in the full cohort (0.87 vs 0.89 m/sec, p=0.2). The interaction of COMT by frailty and COMT by race predicting gait speed were p=0.02 and p=0.01, respectively. Gait speed differences by genotype were significant for frail (n=220, 0.55 vs 0.63 m/sec, p=0.03), but not for pre-frail (n=1691, 0.81 vs 0.81 m/sec, p=0.9), or non-frail (n=1833, 0.98 vs 0.97 m/sec, p=0.7); results were similar in fully adjusted models. Among frail, associations were similar for whites and blacks, but statistically significant for whites only. Associations stratified by clinical cut-offs of gait speed were not significant.
Conclusion: The association of dopamine-related genotype with gait speed is stronger among adults with frailty compared to those without. The potential effects of dopaminergic signaling on preserving physical function in frail adults should be further examined. This is significant to public health as it could improve quality of life of older adults and decrease adverse health outcomes.


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Details

Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Mance, Shannonshm98@pitt.edushm98
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
Committee ChairRosano, Caterinarosanoc@edc.pitt.eduUNSPECIFIEDUNSPECIFIED
Committee MemberRosso, Andreaalr43@pitt.eduUNSPECIFIEDUNSPECIFIED
Committee MemberKammerer, Candacecmk3@pitt.eduUNSPECIFIEDUNSPECIFIED
Date: 31 July 2020
Date Type: Submission
Submission Date: 7 August 2020
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 46
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Uncontrolled Keywords: frailty, gait speed, dopamine, COMT
Date Deposited: 11 Sep 2020 17:13
Last Modified: 11 Sep 2020 17:13
URI: http://d-scholarship.pitt.edu/id/eprint/39584

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