Association of measures of muscle density and snps in homologs of muscle function genes in C. elegans
Başlık çevirisi mevcut değil.
- Tez No: 518025
- Danışmanlar: Dr. CANDACE KAMMERER
- Tez Türü: Yüksek Lisans
- Konular: Genetik, Genetics
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2012
- Dil: İngilizce
- Üniversite: Unıversıty Of Pıttsburgh
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: Belirtilmemiş.
Özet
Özet yok.
Özet (Çeviri)
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 thesis 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 new biological pathways involved in development of sarcopenia.
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