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Association of measures of muscle density and SNPs in homologs of muscle function genes in C.elegans

ALKAN, SEVINC (2012) Association of measures of muscle density and SNPs in homologs of muscle function genes in C.elegans. Master's Thesis, University of Pittsburgh. (Unpublished)

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Sarcopenia, the loss of muscle mass and strength that occurs with aging, has a crucial role in development of frailty. Sarcopenia is recognized as one of the major public health problems affecting approximately 8-40% of individuals greater than age 60 years worldwide. Although sarcopenia and other muscle-related traits are heritable, the underlying genetic variation contributing to the development of sarcopenia is unclear. Previously, researchers identified 18 genes that will delay the onset of sarcopenia in an animal model for aging, Caenorhabditis elegans (Kashyap, 2010), of which 14 have a human homolog and SNP genotypes that were assayed in individuals from the Health, Aging, and Body Composition Study (Health ABC). The primary aim of this study is to assess whether there is a relationship between >700 single nucleotide polymorphisms (SNPs) total in 27 genes [14 genes identified from C. elegans and 13 genes in the mevalonate and ubiquinone pathways] and six traits related to sarcopenia using data from the HealthABC cohort. The 6 outcome variables are isokinetic leg muscle maximum torque( KCTMAX), thigh muscle density(THMUSD), thigh intermuscular fat area(THIMF), total lean mass (TOTLEAN), total percent fat(TOTPF) and thigh total muscle area(THMUS). The European and African American cohort were analyzed separately. After adjusting for the effects of gender, age, and ancestry, single SNP: single trait association tests were performed. Although no SNPs were statistically significant at the experiment-wide p-value (p< 0.00001), SNPs in the locus MAGOHB were associated with THIMF, THMUSD, and TOTPF in European Americans, whereas SNPs in CYP3A5 were associated with these traits in African Americans (p<0.01 for all). Furthermore, SNPs in GOLGA4 (P<0.01) and RALGABP (P<0.001) were associated with TOTPF in African Americans, and SNPs in RALGABP were also associated with THIMF and TOTLEAN in African Americans. These results indicate that variation in some genes related to development of muscle-wasting in an animal model, C. elegans, may have pleiotropic effects on traits related to sarcopenia in older men and women. Follow-up studies of variation in these genes could elucidate the mechanisms involved in development of sarcopenia.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ALKAN, SEVINCsea45@pitt.eduSEA45
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorKAMMERER, CANDACEcmk3@pitt.eduCMK3
Committee MemberFERRELL, ROBERTrferrell@pitt.eduRFERRELL
Committee MemberFISHER, ALFREDafisher@pitt.eduAFISHER
Date: 20 September 2012
Date Type: Completion
Defense Date: 1 August 2012
Approval Date: 20 September 2012
Submission Date: 23 July 2012
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 81
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: SARCOPENIA
Date Deposited: 20 Sep 2012 20:08
Last Modified: 20 Sep 2017 05:15


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