Mutational analysis of KCNJ11 in Chinese elderly essential hypertensive patients

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Author:
Jia-Yue Li(Institute of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China)
Zong-Bin Li(Institute of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China)
Mei Zhu(Institute of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China)
Yu-Qi Liu(Institute of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China)
Yang Li(Institute of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China)
Shi-Wen Wang(Institute of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China)
Qing-Lei Zhu(Institute of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China)
Journal Title:
JOURNAL OF GERIATRIC CARDIOLOGY
Issue:
Volume 09, Issue 02, 2012
DOI:
10.3724/SP.J.1263.2011.12122
Key Word:
Essential hypertension;Phenotype;Genotype;Mutation;The elderly

Abstract: Objective To compare the distribution of KCNJ11 polymorphisms between elderly Chinese population with and without hypertension. Methods We examined the mutation of KCNJ11 gene by directly sequencing. Data for the present study were obtained from 250 hypertensive subjects (60 to 83 years old) as well as 250 normotensive subjects (60 to 86 years old). Results We found nine different mutations in KCNJ11, including six novel mutations (I131M, L147I, L147V, L147L, Q235H, G245C). None of the novel mutations were found in the normotensive subjects, and all the residues were conserved in other species. These sequence variants in Chinese population indicate the diversity of the human library and the complexity of hypertension. Conclusions The consistent finding of our present study provided a basis for the development of new strategies to diagnosis and treat hypertension in the elderly.

  • [1]Staessen JA,Fagard R,Thijs L,et al.Subgroup and perprotocol analysis of the Randomization European Trial on Isolated Systolic Hypertension in the Elderly.Arch Intern Med 1998;158:1681-1691.
  • [2]Gambassi G,Lapane K,Sgadari A,et al.Prevalence,clinical correlates,and treatment of hypertension in elderly nursing home residents.Arch Intern Med 1998;158:2377-2385.
  • [3]Borghi C,Dormi A,D'Addato S,et al.Trends in blood pressure control and antihypertensive treatment in clinical practice:the Brisighella Heart Study.J Hypertens 2004;22:1707-1716.
  • [4]Babenko AP,Aguilar-Bryan L,Bryan J.A view of Sur/KIR6.X,KATP channels.Annu Rev Physiol 1998;60:667-687.
  • [5]Haider S,Antcliff JF,Proks P,et al.Focus on Kir6.2:a key component of the ATP-sensitive potassium channel.J Mol Cell Cardiol 2005;38:927-936.
  • [6]Zingman LV,Hodgson DM,Bast PH,et al.Kir6.2 is required for adaptation to stress.Proc Natl Acad Sci USA 2002;99:13278-13283.
  • [7]Chrissobolis S,Sobey CG.Inwardly rectifying potassium channels in the regulation of vascular tone.Curr Drug Targets 2003;4:281-289.
  • [8]Kane GC,Behfar A,Dyer RB,et al.KCNJ11 gene knockout of the Kir6.2 KATP channel causes maladaptive remodeling and heart failure in hypertension.Hum Mol Genet 2006;15:2285-2297.
  • [9]G(o)gelein H,Hartung J,Englert HC.Molecular basis,pharmacology and physiological role of cardiac K(ATP) channels.Cell Physiol Biochem 1999;9:227-241.
  • [10]Seino S,Miki T.Physiological and pathophysiological roles of ATP-sensitive K+ channels.Prog Biophys Mol Biol 2003;81:133-176.
  • [11]Hansen JB.Towards selective Kir6.2/SUR1 potassium channel openers,medicinal chemistry and therapeutic perspectives.Curr Med Chem 2006;13:361-376.
  • [12]Jeron A,Hengstenberg C,Holmer S,et al.KCNJ11 polymorphisms and sudden cardiac death in patients with acute myocardial infarction.J Mol Cell Cardiol 2004;36:287-293.
  • [13]Koo BK,Cho YM,Park BL,et al.Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population.Diabet Med 2007;24:178-186.
  • [14]Shimomura K.The K(ATP) channel and neonatal diabetes.Endocr J 2009;56:56165-56175.
  • [15]Yamada S,Kane GC,Behfar A,et al.Protection conferred by myocardial ATP-sensitive K+ channels in pressure overloadinduced congestive heart failure revealed in KCNJ11 Kir6.2-null mutant.J Physiol 2006;577:1053-1065.
  • [16]Thomas P,Ye Y,Lightner E.Mutation of the pancreatic islet inward rectifier Kir 6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy.Hum Mol Genet 1996;5:1809-1812.
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