Korean Circulation Journal

  • 제43권1호
  • /
  • Pages.13-22
  • /
  • 2013
  • /
  • 1738-5520(pISSN)
  • /
  • 1738-5555(eISSN)
대한심장학회 (The Korean Society of Cardiology)
권호 표지
DOI QR코드

DOI QR Code

Association between Serine/Threonine Kinase 39 Gene Polymorphism, Hypertension, and Other Cardiovascular Risk Factors in Koreans

  • Shin, Dong-Jik (Cardiovascular Genome Center, Yonsei University Health System) ;
  • Lee, Sang-Hak (Cardiology Division, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine) ;
  • Park, Sungha (Cardiology Division, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine) ;
  • Jang, Yangsoo (Cardiology Division, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine)
  • 발행 : 2013.01.30
⟨ 이전 논문 다음 논문 ⟩

초록

Background and Objectives: Although the association between single nucleotide polymorphisms (SNPs) of Serine/Threonine Kinase 39 (STK39) and hypertension has been reported, the prior studies have been inconsistent. The aim of this study is to evaluate the association between rs3754777 and rs6749447, the two SNPs of STK39, and hypertension and other cardiovascular risk factors in Koreans, residing in the Republic of Korea. Subjects and Methods: We included 238 hypertensive patients and 260 controls. The associations between genotype and haplotype combination and hypertension were examined. In addition, possible SNP-related differences in the adjusted blood pressure and other cardiovascular risk factors were analyzed. Results: There was no significant association between the two SNPs and hypertension. However, the carriers of AA genotype of rs3754777 showed lower blood glucose and cholesterol levels, particularly in females. Genotype of rs6749447 was associated with the waist circumference, triglyceride, and high density lipoprotein-cholesterol levels, only in gender-stratified analysis. The effects of haplotype combinations on risk factors were compatible with genotype effects of each SNP. Conclusion: Associations between the two SNPs of STK39, rs3754777 and rs6749447, and hypertension were not significant. However, the two SNPs showed genotype-related differences in blood glucose, lipids, and waist circumference, especially in women. Further studies are needed to clarify the effect of STK39 variants in these cardiovascular risk factors.

키워드

참고문헌

  1. Wang Y, O'Connell JR, McArdle PF, et al. From the Cover: whole-genome association study identifies STK39 as a hypertension susceptibility gene. Proc Natl Acad Sci U S A 2009;106:226-31. https://doi.org/10.1073/pnas.0808358106
  2. Delpire E, Gagnon KB. SPAK and OSR1: STE20 kinases involved in the regulation of ion homoeostasis and volume control in mammalian cells. Biochem J 2008;409:321-31. https://doi.org/10.1042/BJ20071324
  3. Fava C, Danese E, Montagnana M, et al. Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes. J Hypertens 2011;29:484-91. https://doi.org/10.1097/HJH.0b013e328342b2c1
  4. Chen LY, Zhao WH, Tian W, et al. STK39 is an independent risk factor for male hypertension in Han Chinese. Int J Cardiol 2012;154:122-7. https://doi.org/10.1016/j.ijcard.2010.09.007
  5. Newton-Cheh C, Johnson T, Gateva V, et al. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 2009;41:666-76. https://doi.org/10.1038/ng.361
  6. Levy D, Ehret GB, Rice K, et al. Genome-wide association study of blood pressure and hypertension. Nat Genet 2009;41:677-87. https://doi.org/10.1038/ng.384
  7. Cunnington MS, Kay C, Avery PJ, Mayosi BM, Koref MS, Keavney B. STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression. BMC Med Genet 2009;10:135. https://doi.org/10.1186/1471-2350-10-135
  8. Niu WQ, Zhang Y, Ji KD, Gao PJ, Zhu DL. Contribution of five top whole- genome association signals to hypertension in Han Chinese. J Hum Hypertens 2011;25:278-80. https://doi.org/10.1038/jhh.2010.114
  9. Rhee MY, Yang SJ, Oh SW, et al. Novel genetic variations associated with salt sensitivity in the Korean population. Hypertens Res 2011;34: 606-11. https://doi.org/10.1038/hr.2010.278
  10. Mooser V, Waterworth D, Song KJ, Yuan X, Knouff CW, inventors; GlaxoSmithKline Crop., assignee. Metabolic syndrome genetics. United States patent US 0203012 A1. 2009 Aug 13
  11. Johnston AM, Naselli G, Gonez LJ, Martin RM, Harrison LC, DeAizpurua HJ. SPAK, a STE20/SPS1-related kinase that activates the p38 pathway. Oncogene 2000;19:4290-7. https://doi.org/10.1038/sj.onc.1203784
  12. Piechotta K, Garbarini N, England R, Delpire E. Characterization of the interaction of the stress kinase SPAK with the Na+-K+-2Cl- cotransporter in the nervous system: evidence for a scaffolding role of the kinase. J Biol Chem 2003;278:52848-56. https://doi.org/10.1074/jbc.M309436200
  13. Lee J, Sun C, Zhou Y, et al. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nat Med 2011;17:1251-60. https://doi.org/10.1038/nm.2449
  14. Kushiyama A, Shojima N, Ogihara T, et al. Resistin-like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet. J Biol Chem 2005;280:42016-25. https://doi.org/10.1074/jbc.M503065200
  15. Ruixing Y, Jinzhen W, Shangling P, Weixiong L, Dezhai Y, Yuming C. Sex differences in environmental and genetic factors for hypertension. Am J Med 2008;121:811-9. https://doi.org/10.1016/j.amjmed.2008.04.026
  16. Qi H, Labrie Y, Grenier J, Fournier A, Fillion C, Labrie C. Androgens induce expression of SPAK, a STE20/SPS1-related kinase, in LNCaP human prostate cancer cells. Mol Cell Endocrinol 2001;182:181-92. https://doi.org/10.1016/S0303-7207(01)00560-3

피인용 문헌

  1. Genetics of Human Primary Hypertension: Focus on Hormonal Mechanisms vol.40, pp.3, 2013, https://doi.org/10.1210/er.2018-00071