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PPARGC1A Variation Associated With DNA Damage, Diabetes, and Cardiovascular Diseases.
- Source :
-
Diabetes . Apr2008, Vol. 57 Issue 4, p809-816. 8p. 2 Diagrams, 5 Charts, 1 Graph. - Publication Year :
- 2008
-
Abstract
- OBJECTIVE--Individuals with type 2 diabetes exhibit higher DNA damage and increased risk of cardiovascular disease (CVD). However, mechanisms underlying the association between DNA damage and development of type 2 diabetes and CVD are not understood. We sought to link peroxisome proliferator-activated receptor-γ coactivator-1 α (PPARGC1A), a master transcriptional regulator of mitochondrial oxidative phosphorylation and cellular energy metabolism, with DNA damage, type 2 diabetes, and CVD. RESEARCH DESIGN AND METHODS--We measured DNA damage as urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration and examined the relationship between nine PPARGC1A genetic variants, DNA damage, type 2 diabetes, and self-reported CVD in 959 participants of the Boston Puerto Rican Health Study. RESULTS--With respect to urinary 8-OHdG, PPARGC1A variants showed significant association, and PPARGC1A haplotypes exhibited significant association after correction for multiple testing. Two independent PPARGC1A variants associated significantly with type 2 diabetes (odds ratios [ORs] 1.35 and 2.46; P = 0.045 and <0.001). Carriers of minor alleles of two other PPARGC1A variants, both in strong linkage disequilibrium and associated with lower DNA damage, showed lower prevalence of CVD (ORs 0.53 and 0.65; P = 0.030 and 0.175). Moreover, we found that physical activity correlated negatively with DNA damage. CONCLUSIONS--It is plausible that low physical activity combined with risk haplotyes contribute to the high prevalence of type 2 diabetes in this population. We propose that PPARGC1A influences development of type 2 diabetes and CVD via DNA damage. Increasing physical activity, which induces PPARGC1A expression, is a potential strategy to slow DNA damage, thereby decreasing the risk of CVD for individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PEROXISOMES
*DNA damage
*TYPE 2 diabetes
*DIABETES
*CARDIOVASCULAR diseases
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 57
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 31824521
- Full Text :
- https://doi.org/10.2337/db07-1238