Abstract
BackgroundEssential hypertension is associated with mitochondrial dysfunction. Because mitochondrial dynamics; mitochondrial morphological changes are closely linked with various mitochondrial functions, we aimed to examine whether the genetic variation of the mitochondria-shaping genes influenced the susceptibility to blood pressure (BP) and hypertension.MethodsThe quantitative BP trait analysis and hypertension case-control analysis for the total 52 single-nucleotide polymorphisms (SNPs) in the five major mitochondria-shaping genes were performed in the Korean Association Resource (KARE) study cohort (8,512 subjects).ResultsIn the total subjects of the KARE study cohort, there were no statistically significant associations of the SNPs in the five mitochondria-shaping genes with BP or hypertension after adjusting for multiple tests. However, the age group analysis in the 40s, 50s, and 60s age subgroups revealed that 15 SNPs out of 26 SNPs genotyped in the OPA1 gene were significantly associated with BP and/or hypertension in the 60s age subgroup and their association P values satisfied the Bonferroni-corrected significance level (P 0.00625). Noticeably, nine SNPs were consistently associated with all the three traits; systolic BP (SBP), diastolic BP (DBP), and hypertension. In silico lookup of the associated SNPs in the Southern German population did not reveal associations with BP traits.ConclusionsOur results indicate that genetic variation of the mitochondrial fusion-regulating gene, OPA1, might be associated with BP and hypertension in an age-dependent and population-specific manner in the Korean study cohort, and suggest that altered mitochondrial dynamics, especially involved in the mitochondrial fusion event, may play an important role in the pathogenesis of hypertension.
| Original language | English |
|---|---|
| Pages (from-to) | 1127-1135 |
| Number of pages | 9 |
| Journal | American Journal of Hypertension |
| Volume | 24 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2011 |
Bibliographical note
Funding Information:Supplementary material is linked to the online version of the paper at http:// www.nature.com/ajh Acknowledgment:this work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and technology (2009-0075599, 2009-0093189, and KRF-2008-313-c00673). the clinical information and genotype data were provided by the KARE and KORA studies.the KARE study was supported by center for Genome Science, the Korea National Institute of Health, Korea center for Disease control, Ministry for Health, Welfare and Family Affairs (the Korean Genome Analysis Project (4845-301)). the KORA 500K blood pressure study was supported byWellcometrust International Senior Research Fellow (grant no. 070191/Z/03/Z) in Biomedical Science in central Europe, by Alexander-von-Humboldt Foundation partnership (grant no.V-Fokoop-ESt/1051368,V-Fokoop-1113183) and by Estonian Ministry of Education and Science core grant no. 0182721s06 (to M.L.). the KORA Augsburg studies were financed by the Helmholtz Zentrum München, German Research center for Environmental Health, Neuherberg, Germany and supported by grants from the German Federal Ministry of Education and Research (BMBF). the KORA study group consists of H.-E. Wichmann (speaker), A. Peters, c. Meisinger, t. Illig, R. Holle, J. John, and co-workers who are responsible for the design and conduct of the KORA studies.
Keywords
- OPA1
- blood pressure
- genetics
- hypertension
- mitochondria-shaping gene
- mitochondrial dynamics
- single-nucleotide polymorphism