DOI QR코드

DOI QR Code

Association of PPARGC1A Gene Variants with Hypertension in Korean Population

  • Jin, Hyun-Seok (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Park, Sangwook (Department of Biomedical Laboratory Science, College of Health and Medical Science, Sangji University)
  • Received : 2021.02.24
  • Accepted : 2021.03.25
  • Published : 2021.03.31

Abstract

Hypertension (HTN) is one of the cardiovascular disease risk factors. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC1A) is involved in a master modulator of mitochondrial biogenesis, and pulmonary arterial hypertension. In this study, we report results of PPARGC1A were associated with hypertension and its intermediate phenotype of systolic (SBP) and diastolic blood pressure (DBP) in the Korean population. In detail, identifying a susceptibility locus, 3 SNPs for HTN, 2 SNPs for SBP, 3 SNPs for DBP at P<0.05. Among them, rs1472095 in PPARGC1A gene statistically demonstrated one of the significant correlations with Hypertension (P-value=0.00359, OR=0.8, 95% CI=0.68~0.93). The minor allele (T) of PPARGC1A was statistically associated with the increased value of DBP, SBP, and the increase risk of hypertension. We aim to manifest a significant association between genetic variant in PPARGC1A and hypertension. This finding suggested that association of PPARGC1A genetic polymorphism and HTN accelerates our understanding of blood pressure control and underlines potential drug targets for treatment of hypertension.

Keywords

References

  1. Ahmetov II, Fedotovskaya ON. Current Progress in Sports Genomics. Adv Clin Chem. 2015. 70: 247-314. https://doi.org/10.1016/bs.acc.2015.03.003
  2. Cabrera CP, Ng FL, Nicholls HL, Gupta A, Barnes MR, Munroe PB, et al. Over 1000 genetic loci influencing blood pressure with multiple systems and tissues implicated. Hum Mol Genet. 2019. 21; 28: R151-R161.
  3. Carretero OA, Oparil S. Essential hypertension. Part I: definition and etiology. Circulation. 2000. 101: 329-335. https://doi.org/10.1161/01.CIR.101.3.329
  4. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ, et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet. 2009. 41: 527-534. https://doi.org/10.1038/ng.357
  5. El Rouby N, McDonough CW, Gong Y, McClure LA, Mitchell BD, Horenstein RB, et al. Genome-wide association analysis of common genetic variants of resistant hypertension. Pharmacogenomics J. 2019. 19: 295-304. https://doi.org/10.1038/s41397-018-0049-x
  6. Healthcare Bigdata, and Health Insurance Review & Assessment Service, 2019 http://opendata.hira.or.kr/op/opc/olapMfrnIntrsIlnsInfo.do
  7. Ingelsson E, Bennet L, Ridderstrale M, Soderstrom M, Rastam L, Lindblad U. The PPARGC1A Gly482Ser polymorphism is associated with left ventricular diastolic dysfunction in men. BMC Cardiovasc Disord. 2008. 8: 37. https://doi.org/10.1186/1471-2261-8-37
  8. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005. 365: 217-223. https://doi.org/10.1016/S0140-6736(05)70151-3
  9. Li TT, Tan TB, Hou HQ, Zhao XY. Changes in peroxisome proliferatoractivated receptor alpha target gene expression in peripheral blood mononuclear cells associated with non-alcoholic fatty liver disease. Lipids Health Dis. 2018.17: 256. https://doi.org/10.1186/s12944-018-0901-7
  10. Marcus JH, Novembre J. Visualizing the geography of genetic variants. Bioinformatics. 2017. 33: 594-595. https://doi.org/10.1093/bioinformatics/btw643
  11. Martinez-Redondo V, Pettersson AT, Ruas JL. The hitchhiker's guide to PGC-1alpha isoform structure and biological functions. Diabetologia. 2015. 58: 1969-1977. https://doi.org/10.1007/s00125-015-3671-z
  12. Pan S, Naruse H, Nakayama T. Progress and issues of the genome-wide association study for hypertension. Curr Med Chem. 2015. 22: 1016-1029. https://doi.org/10.2174/0929867321666141216124537
  13. Petr M, Maciejewska-Skrendo A, Zajac A, Chycki J, Stastny P. Association of Elite Sports Status with Gene Variants of Peroxisome Proliferator Activated Receptors and Their Transcriptional Coactivator. Int J Mol Sci. 2019. 21: 162. https://doi.org/10.3390/ijms21010162
  14. Popov DV. Adaptation of Skeletal Muscles to Contractile Activity of Varying Duration and Intensity: The Role of PGC-1α. Biochemistry (Mosc). 2018. 83: 613-628. https://doi.org/10.1134/S0006297918060019
  15. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998. 92: 829-839. https://doi.org/10.1016/S0092-8674(00)81410-5
  16. Qiu L, Fan X, Zhang Y, Teng X, Miao Y. Molecular characterization, tissue expression and polymorphisms of buffalo PPARGC1A gene. Arch Anim Breed. 2020. 63: 249-259. https://doi.org/10.5194/aab-63-249-2020
  17. Singh M, Singh AK, Pandey P, Chandra S, Singh KA, Gambhir IS. Molecular genetics of essential hypertension. Clinical and Experimental Hypertension. 2016. 38: 268-277. https://doi.org/10.3109/10641963.2015.1116543
  18. Sinha RA, Rajak S, Singh BK, Yen PM. Hepatic Lipid Catabolism via PPARα-Lysosomal Crosstalk. Int J Mol Sci. 2020. 21: 2391. https://doi.org/10.3390/ijms21072391
  19. Vargas-Sanchez K, Vargas L, Urrutia Y, Beltran I, Rossi AB, Lozano HY, et al. PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population. J Inflamm (Lond). 2020. 17: 35. https://doi.org/10.1186/s12950-020-00264-2
  20. Vimaleswaran KS, Luan J, Andersen G, Muller YL, Wheeler E, Brito EC, et al. The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals. J Appl Physiol (1985). 2008. 105:1352-1358. https://doi.org/10.1152/japplphysiol.90423.2008
  21. Warren HR, Evangelou E, Cabrera CP, Gao H, Ren M, Mifsud B, et al. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nat Genet. 2017. 49: 403-415. https://doi.org/10.1038/ng.3768
  22. World Health Organization. A Global Brief on Hypertension: Silent Killer, Global Public Health Crisis. Geneva, Switzerland: World Health Organization, 2013.
  23. Yeligar SM, Kang BY, Bijli KM, Kleinhenz JM, Murphy TC, Torres G, et al. PPARγ Regulates Mitochondrial Structure and Function and Human Pulmonary Artery Smooth Muscle Cell Proliferation. Am J Respir Cell Mol Biol. 2018. 58: 648-657. https://doi.org/10.1165/rcmb.2016-0293OC