摘要
目的：研究心钠素基因第3外显子上ScaⅠ酶切位点T2238C多态性、第2内含子上HpaⅡ酶切位点G1837A多态性以及这2个单核苷酸多态性(SNP)构成的单体型在新疆哈萨克族人群中的分布特点，探讨心钠素基因SNP及单体型与新疆哈萨克族原发性高血压的相关关系。方法：采用整群抽样随机抽取方式，以生活在新疆塔城地区和丰县、阿尔泰地区福海县和伊犁地区新源县的30岁以上的定居和半定居的哈萨克族牧民543人为研究对象，进行标准化的问卷调查、体格检查。经流行病学问卷调查和体检后，按照WHO／ISH 1999年的高血压诊断标准，收缩压(SBP)均值≥140mmHg和／或舒张压(DBP)均值≥90mmHg及正在服用降压药物者为高血压组(EH组)；共检出314例，其中男性128例，女性186例，平均年龄49.31±11.01岁。SBP＜140mmHg和DBP＜90mmHg者229例为血压正常的对照组(NT组)，其中男性107例，女性122例，平均年龄40.46±10.81岁。采用经典的蛋白酶K消化、饱和酚／氯仿抽提法提取外周血白细胞基因组DNA，聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法，检测所有研究对象的心钠素基因T2238C、G1837A基因型。分析EH组和NT组中各基因型、等位基因及单体型的频率分布特点，比较两组之间、各基因型携带者之间、2个SNP组成的联合基因型之间血压、血脂、血、尿电解质的差别及其与高血压的相关性。结果：1)新疆哈萨克族人群心钠素基因T2238C位点存在TT、TC和CC三种基因型和T、C两种等位基因。三种基因型在EH组和NT组中的频率分别为
Objective: To investigate the relationship between ANP gene T2238C, G1837A single nucleotide polymorphism (SNP), gene haplotype and essential hypertension in Xinjiang Kazakhs. Methods: 543 Xinjiang Kazakhs were recruited in our study. They were divided into 314 hypertensives (EH group) whose SBP>140mmHg and/or DBP> 90mmHg and 229 normotensives (NT group) whose BP<140/90mmHg. We measured their ANP gene T2238C, G1837A polymorphism by.PCR-RFLP method and tested the association of the polymorphism and heplotype with hypertension. Results: 1) We detected three kinds of genotype and two kinds of allele of ANP gene T2238C polymorphism. The frequencies of three kinds of genotype TT, TC, CC were 0.87, 0.11, 0.02 in hypertensive patients and 0.91, 0.08, 0.01 in controls respectively. The frequencies of two kinds of allele T and C were 0.93, 0.07 in hypertensives and 0.95, 0.05 in controls respectively. We also detected three kinds of genotype and two kinds of allele of G1837A polymorphism. The frequencies of genotype GG, GA and AA were 0.79, 0.20, 0.01 in hypertensives and 0.83, 0.16, 0.01 in controls respectively. The frequencies of G and A allele were 0.89, 0.11 in hypertensives and 0.91, 0.09 in controls respectively. 2) Both of genotype and allele frequencies of T2238C and G1837A had no significant differences between two groups (x~2 =2.013, P=0.36 and x~2 =1.022, P=0.312; x~2 =2.249, P=0.13 and x~2 =0.583, P=0.445 respectively). 3) We did not find association of 2238C allele with
引文
[1] 孙佳艺，赵冬，王薇，等．北京地区2 740人的血压水平10年(1992-2002)变化情况[J]．高血压杂志．2005，13(2)：115-119
[2] 高路，闫伟，杨智丽，等．云南省哈尼族高血压患病情况调查分析[J]．高血压杂志．2004，12(4)：362-364
[3] 刘忠仁．我国各地高血压流行病学调查近况[J]．医学综述．2004，10(2)：88-89
[4] 吴桂贤，吴兆苏，王薇，等．1992-2002年北京一组队列人群心血管病危险因素变化趋势研究[J]．中华心血管病杂志．2005，33(8)：748-753
[5] 袁宝君，潘晓群，史祖民，等．江苏省高血压患病率及相关因素流行病学研究[J]．江苏预防医学．2004，15(3)：3-5
[6] 孙瑛，祖淑玉，徐成丽．等．北京市区2382名学生血压水平及相关因素分析[J]．北京医学．2004，27(7)：422-425
[7] 中华人民共和国卫生部，中华人民共和国科学技术部，中华人民共和国科学统计局．中国居民营养与健康现状[J]．中国心血管病研究杂志．2004，2：919-922
[8] 中国人群心血管病危险因素作用特点的前瞻性研究[J]．中华流行病学杂志．2005，26(1)：58-61
[9] Fuentes RM, Notkolaa IL, Shemeikka S, et al. Familial aggregation of blood pressure[J]. J Hum Hypertens. 2000, 14: 441-445
[10] Oshaughnessy KM, The Genetics of Essential Hypertension[J]. Br J Clin Pharmaco. 2001, 151: 5-11
[11] Tanira MOM, Balushi KA Al. Genetic variations related to hypertension: a review[J]. Journal of Human Hypertension. 2005, 19: 7-19
[12] Dominiczak AF, Negrin DC, Clark JS, et al. Genes and Hypertension[J]. Hypertension. 2000, 35: 164-172
[13] Ian Phillips M. Is gene therapy for hypertension possible?[J].??Hypertension. 1999, 33: 8-13
[14] 王佐广，温绍君，吴兆苏．高血压基因治疗研究进展[J]．生理科学进展．2001，32(4)：312-316
[15] 孙琦，柳青，雷寒。原发性高血压候选基因研究进展[J]．重庆医学．2003，32(10)：1422-1424
[16] 朱鼎良．我国高血压基因研究十年回顾和几点建议．中华心血管病杂志．2005，33(7)：585-587
[17] 狄群，占伊扬．原发性高血压候选基因的研究进展[J]．中国全科医．2002，5(2)：158-160
[18] Robinsonl M, Williams SM. Role of two angiotensinogen polymorphisms in blood pressure variation[J]. Journal of Human Hypertension. 2004, 18: 865-869
[19] 孔祥东，杨宇霞．简化的血管紧张素原基因单倍型分析与原发性高血压的关系[J]．临床内科杂志．2005，22：495-497
[20] 刘艳，金玮，姜正文，等．血管紧张素原基因的六种单核苷酸多态与原发性高血压的相关性[J]．中华遗传学杂志．2004，21：116-119
[21] Zhu X. Linkage disequilibrium and haplotype diversity in the genes of the renin-angiotensin system: findings from the family blood pressure program[J]. Genome Res. 2003, 13: 173-181
[22] Zhu X. Associations between hypertension and genes in the renin-angiotensin system[J]. Hypertension. 2003, 41: 1027-1034
[23] 何虹，汪涛，臧益民．盐敏感性高血压的相关因素[J]．心脏杂志．2004，16(1)：83-85
[24] 李玉明，盐敏感性高血压：历史、现状、展望[J]．中华心血管病杂志．2003，31(12)：955-957
[25] De Wardener HE, MacGregor GA. Sodium and blood pressure[J]. Curt Opin Cardiol. 2002, 17: 360-367
[26] 温绍君，张维君，王金城，等．心包心钠素的基因表达[J]．中华心血管病杂志 1999；27(5)：345
[27] Weidmann P, hasler L, Gnadinger MP, et al. Blood levels and renal effects of atrial natriuretic peptide in normal man[J]. J Clin Invest. 1986, 77:734-742
[28] Loutzenhiser R, Hayashi K, Epstein M. Atrial natriuretic peptide reverses afferent arteriolar vasoconstriction and potentiates efferent arteriolar vasoconstriction in the isolated perfused rat kidney [J]. Journal of Pharmacology and Experimental Therapeutics. 1988, 246(2):522-588
[29] Huang CL, Lewicki J, Johnson LK, et al. Renal mechanism of action of rat atrial natriuretic factor[J]. J Clin invest. 1988, 75:769-773
[30] Huang CL, Lewicki J, Johnson LK, et al. Renal mechanism of action of rat atrial natriuretic factor[J]. J Clin invest. 1988, 75:769-773
[31] Focacio A, Volpe M, Ambrosio G, et al. Angiotensin II directly stimulates release of atrial natriuretic factor in isolated rabbit hearts [J]. Circulation.1993, 87: 192-198
[32] Franco-Saenz R, Somani P, Mulrow PJ. Effect of atrial natriuretic peptide(8-33-metAN P)in patients with hypertension[J]. American Journal of Hypertension. 1992, 5: 266-275
[33] Lin KF, Chao J, Chao L. Atrial natriuretic peptide gene delivery reduces stroke-induced mortality rate in Dahl salt-sensitive rats[J]. Hypertension. 1999,33:219-224
[34] Baxter GF. The natriuretic peptides: An introduction[J]. Basic Res Cardiol. 2004,99: 71-75
[35] Cheung BMY, Chir MBB, Kumana CR, et al. Natriuretic peptides- relevance in cardiovascular disease[J]. JAMA. 1998, 280(23): 1983- 1984
[36] Raji A, Williams GH, Jeunemaitre X.Insulin resistance in hypertensives:effect of salt sensitivity,renin status and sodium intake[J]. J Hypertens.2001,19:99-105
[37] Milan A, Mulatero P, Rabbia F, et al. Salt intake and hypertensiontherapy[J]. J Nephrol.2002,15:1-6
[38] Suter PM, Sierro C, Vetter W. Nutritional factors in the control of blood pressure and hypertension[J]. Nutr din Care.2002,5:9-19
[39] Melander O, Frandsen E.Plasma ProANP(1-30)reflects salt sensitivity in subjecs with heredity for hypertension[J]. Hypertension. 2002,39(5):996-999
[40] Kinugawa T, Endo A, Kato M, et al. Responses of plasma catecholamines, rennin-angiotensin-aldosterone system and atrial natriuretic peptide to exercise in patients with essential hypertension[J]. Cardiology. 1997,88:238-245
[41] Ruskoaho H. Atrial natriuretic peptide: synthesis, release, and metabolism[J]. Pharmacol Rev.1992,44: 479-602
[42] Wijeyaratne CN, Moult PJA. The effect of a human atrial natriuretic peptide on plasma volume and vascular permeability in normotensive subjects[J]. Journal of Clinical Endocrinology and Metabolism. 1993,76:343-346
[43] John S W M, Krege J H, Oliver P M, et al. Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension [J]. Science. 1995, 267: 679-681
[44] Yang-Feng T L, Floyd-Smith G, Nemer M,et al. The pronatriodilatin gene is located on the distal short arm of human chromosome 1 and on mouse chromosome 4[J]. Am J Hum Genet. 1985,37: 1117-1128
[45] Greenberg BD, Bencen GH, Seilhamer JJ, et al. Nucleotide sequence of the gene encoding human atrial natriuretic factor precursor[J]. Nature. 1984,312:656-658
[46] Roussel R, Tregouet DA, Hadjadj S, et al. Investigation of the HumanANPGene in Type 1 Diabetic Nephropathy Case-Control and Follow-up Studies[J]. Diabetes. 2004,53(5):1394-1398
[47] Masharani U, Nakashima P F, Lim D W, et al. Nsil and Scalrestriction fragment length polymorphisms at atrial natriuretic peptide(ANP)gene locus[J]. Hum Genet. 1988, 80: 307
[48] Ramasawmy R, Kotea N, Lu C, et al. Investigation of the polymorphic Seal site by a PCR-based assay at the human atrial natriuretie peptides(hANP)gene locus[J]. Hum Genet. 1992, 90: 323-324
[49] Rutledge D R, Sun Y, Ross E A. Polymorphisms within the atrial natriuretie peptide gene in essential hypertension[J]. J Hypertens. 1995, 13: 953-955
[50] Kato N, Sugiyama T, Morita H, et al. Genetic analysis of the atrial natriuretic peptide gene in essential hypertension[J]. Clin Sci. 2000, 98: 251-258
[51] Nannipieri M, Manganiello M, Pezzatini A, et al. Polymorphisms in the hANP(Human Atrial Natriuretie Peptide)Gene, Albuminuria, and Hypertension[J]. Hypertensio. 2001, 37: 1416-1422
[52] 杨丽姝，刘晓民，潘尚哈，等．心钠素基因T2238C多态性与2型糖尿病肾病易感性的相关性研究[J]．黑龙江医学．2004，28：414-416
[53] Ciechanowiez A, Kurzawski G, Wideeka K, et al. Mutation T→C of nucleotide 2238 in the gene of atrial natriuretie peptide(ANP) precursor and heterogeneity of sodium-sensitive hypertension: Preliminary report[J]. Pol Arch Med Wewn. 1997, 98: 501-509
[54] Nannipieri M, Penno G, Pueci L, et al. Pronatriodilatin gene polymorphisms, mierovascular permeability, and diabetic nephropathy in type 1 diabrtes mellitus[J]. J Am Soe Nephrol. 1999, 10: 1530-1541
[55] Ramasawmy R, Kotea N, Lu C, et al. A new polymorphie restriction site at the human atrial natriuretic peptide(hANP)gene locus[J]. Hum Genet. 1993, 91: 509-510
[56] Cheung BMY, Leung R, Shiu S, et al. HpalI polymorphism in the??atrial natriuretic peptide gene and hypertension[J]. Am J Hypertens. 1999, 12: 524-527
[57] Schorr U, Beige J, Ringel J, et al. Hpall polymorphism of the atrial natriuretic peptide gene and the blood pressure response to salt intake in normotensive men[J]. J Hypertens. 1997, 15: 715-718
[58] Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing hypertsion in middle-aged women and men: The Framingham Heart study[J]. JAMA. 2002, 287: 1003-1010
[59] Dzida G et al. Polymorphisms of angiotensin-converting enzyme and angiotensin Ⅱ receptor type 1 genes in essential hypertension in a Polish population[J]. J Med Sci Monit. 2001, 7(6): 1236-1241.
[60] Mein CA, Caulfield, Dobson RJ, et al. Genetics of esseential hypertension[J]. Human Molecular Genetics. 2004, 13: R169-R175
[61] 徐新娟，汪师贞．新疆地区高血压流行病学调查研究回顾[J]．新疆医科大学学报．2004，27(3)：312-314
[62] 夏晓利，别革兰，路航，等．新疆哈萨克族、汉族高血压调查分析[J]．高血压杂志．2000，8(4)：283-284
[63] 张明涛，陈平虎．汉、哈两民族农民中高血压患病情况及血压值比较分析[J]．中华流行病学杂志．1984，5(1)：29-34
[64] 汪师贞，马依彤，程祖亨，等．限制哈萨克族高血压患者盐摄入量的降压效应观察[J]．中国慢性病预防与控制．1994，2(4)：167-170
[65] 李南方，周玲，曹梅，等．新疆和丰县牧区高血压病流行病学调查报告[J]．现代预防医学．2003，30(2)：141-143
[66] 李南方，周玲，董旭南，等．新疆哈萨克族人的血管紧张素原基因的T174M多态性与高血压病的相关性研究[J]．中华心血管病杂志．2003，31(10)：726
[67] 李南方，周玲，殷晓娟，等．新疆哈萨克族人血管紧张素原基因M235T多态性与原发性高血压相关性研究[J]．科学技术与工程．2004，4(3)：193-197[68] 李南方，周玲，吴卫东，等．血管紧张素原基因5′端核心启动子区(-6)A-G和(-20)A-C变异与哈萨克族人原发性高血压相关性分析[J]．中华医学遗传学杂志．2004，21(1)：23-28
[69] 李南方，李红建，周玲，等．α-adducin基因变异与新疆哈萨克族人原发性高血压的相关研究[J]．科学技术与工程．2004，4(7)：551-555
[70] 李南方，骆秦，周玲，等．β_2肾上腺素能受体基因+46位Arg16／Gly多态性与新疆哈萨克族人群低密度脂蛋白胆固醇水平的关系[J]．中华心血管病杂志．2005(12)：1071-1074
[71] 刘辉，李南方，李涛，等．β_2肾上腺素能受体基因Gln27Glu多态性与新疆哈萨克族原发性高血压的相关研究[J]．临床心血管病杂志．2005，(21)：426-429
[72] Levin ER, Gardner DG, Samson WK. Natriuretic Peptide[J]. N Engl J Med. 1998, 339: 321-328
[73] WHO MONICA Project(Monitoring Trends and Determinants in Cardiovascular Disease): A major international Collaboration[J]. J Clin Epideiol. 1988, 41: 105-114
[74] de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats[J]. Life Sci. 1981; 28: 89-94
[75] de Bold AJ Tissue fractionation studies on the relationship between an atrial natriuretic factor and specific atrial granules[J]. Can J Physiol Pharmacol. 1982, 60: 324-330
[76] Flynn TG, de Bold ML, de Bold AJ.The amino acid sequence of an atrial peptide with potent diuretic and natriuretic properties[J]. Bioc, hem Biophys Res Commun. 1983, 117: 859-865
[77] Kangawa K, Matsuo H. Purification and complete amino acid sequence of α-human atrial natriuretic polypeptide(α-hANP)[J]. Biochem Biophys Res Commun. 1984; 118: 131-139
[78] Nannipieri M, Posadas R, Williams K, et al. Asssociation between??polymorphisms of the Atrial Natriuretic Peptide gene and proteinuria: a population-based study[J]. Diabetologia. 2003, 46: 429-432
[79] 王笑峰，汪师贞，林仁勇，等．新疆哈萨克族隔离群血管紧张素转换酶基因I／D多态性与高血压病的关系[J]．中华医学遗传学杂志．2003，20(3)：253-255
[80] 张朝霞，刘燕，林仁勇，等．新疆哈萨克族ADD1基因Glv／460Trp多态性与高血压病的关联[J]．复旦学报(医学版)．2005，32(2)：239-242
[81] 李南方，张艳敏，李涛，等．新疆哈萨克族原发性高血压与心钠素基因T2238C多态性的相关关系[J]．临床心血管病杂志．2005，21：513-515
[82] Roussel, Tregouet DA, Hadjadj S, et al. Investigation of the HumanANPGene in Type 1 Diabetic Nephropathy. Case-Control and Follow-up Studies[J]. Diabetes. 2004, 53: 1394-1398
[83] 汪师贞，张月明，程祖亨．新疆维吾尔族自治区不同民族高血压流行病学因素[J]．中国心血管病杂志．1984，12(1)：179
[84] 赵光胜，汪师贞，袁晓源，等．营养、代谢与高血压[J]．中华心血管病杂志．1986，14(1)：8-13
[85] Vasan RS, Betser A, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: the Framingham Heart Study[J]. JAMA. 2002, 287: 1003-1010
[86] Stanley SF, Milagros JJ, Nathan DW, et al. Predominance of isolated systolic hypertension among middle-aged and elderly hypertensives[J]. Hypertension. 2001, 37: 869
[87] Steinhelper ME, Cochrane KL, Field LJ. Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes[J]. Hypertension. 1990, 16: 301-307
[88] Rubattu S, Ridker P, Stampfer MJ, et al. The gene encoding atrial natriuretic peptide and the risk of human stroke[J]. Circulation.??1999, 100: 1722-1726
[89] Zhou BF, Wu YF, Yang J, et al. Overweight is an independent risk factor for cardiovascular disease in Chinese population[J]. Obesity Review. 2002, 3: 147-156
[90] Sacks FM, Appel LJ, Moore TJ, et al. A dietary approach to prevent hypertension: a review of the dietary approaches to stop hypertension(DASH)study[J]. Clin Cardiol. 1999, 22(7): 6-10
[91] 王中群，吕全军，裴迎新，等．原发性高血压与膳食及其他相关因素的关系[J]．中国动脉硬化杂志．2004，12(4)：461-465
[92] 傅世英，曹雅民，李耀平．黑龙江省高血压病流行病学的研究[J]．中华内科杂志，2002，41(2)：114-117
[93] 何秉贤，朱徐，黄定，等．新疆汉、维吾尔、哈萨克三民族高血压流行病学调查[J]．新疆医学．1992，22(4)：194-201
[94] 张明涛，王兰．青少年学生血压分布于体格发育的关系[J]．中华心血管病杂志．1994，22(2)：99-101
[95] 刘华，史正萍，李喆．肥胖在哈汉两组高血压患者中致病特点的分析[J]．心肺血管病杂志．2000，19(2)：81-83
[96] 赵连成，周北凡，武阳丰，等．体重指数与死亡的前瞻性研究[J]．中华流行病学杂志．2002，23：24-27
[97] 邹阳春，何秉贤，胡大一．新疆哈、汉两民族血脂、脂蛋白A及载脂蛋白AI和B水平的比较与相关研究[J]．中国动脉硬化杂志．2001，9(4)：340-344
[98] 谷杨，马雅静，程江．435例哈萨克族、汉族牧区与市区居民血脂调查分析[J]．检验医学．2005，20(4)：342-343
[99] 崔国方，刘华，艾丽曼，等．新疆阿勒泰地区哈、汉两民族高血压及正常血压者血脂与血糖．胰岛素间相关关系的研究[J]．新疆医学院学报．1998，20(2)：126-129
[100] 李莹，陈志红，周北凡，等．血脂和脂蛋白水平对我国中年人群缺血性心血管病事件的预测作用[J]．中华心血管病杂志，2004，32：643-647[101] Weder AB. Membrane sodium transport and salt sensitivity of blood pressure. Hypertension, 1991, 17(1 Supp 1): 174-180
[102] Marcano AC, Onipinla AK, Caulfield MJ, et al. Recent advances in the identification of genes for human hypertension[J]. Expert Rev Cardiovasc Ther. 2005, 3(4): 733-41
[103] Sharma AM, Jeunemaitre X. The future of genetic association studies in hypertension: improving the signal-to-noise ratio[J]. J Hypertens. 2000, 18: 811-814
[104] Mooser V, Waterworth DM, Isenhour T, et al. Cardiovascular pharmacogenetics in the SNP era[J]. J Thramb Hacmost. 2003, 1: 1398-1402
[105] Becker N, Nieters A, Rittgen W. Single nucleotide polymorphismdisease, relationships: statisticalissues for the performance of association studies[J]. Murat Res. 2003, 15: 11-18
[106] Salisbury BA, Pungliya M, Choi JY, et al. SNPand haplotype variation in the human genome[J]. Mutat Res. 2003, 15: 53-61
[107] Zhao JH, Curtis D, Sham PC. Model-free analysis and permutation tests for allelic associations[J]. Hum Hered. 2000, 50: 133-139
[108] Schmith VD, Campbell DA, Sehgal S, et al. Pharmacogenetics and disease genetics of complex disease[J]. Cell Mol Life Sci. 2003, 60: 1636-1646
[109] Harrp SB. Where are all the blood-pressure genes?[J] Lancet. 2003, 61: 2149-2151
[110] Moore JH, Williams SM. New strategies for identifying gene-gene interactions in hypertension[J]. Ann Med. 2002, 34: 88-95
[111] 梁云，周韧．人类基因组中的连锁不平衡方式[J]．国外医学．生理、病理科学与临床分册．2005，25：247-250
[112] Kruglyak L. Prospects for whole-genome genome linkage disequilibrium mapping of common disease genes[J]. Nat. Genet. 1999, 22: 139-144[113] Slager S, Huang J, Vieland VJ. Effect of allelic hetero-geneity on the power of the transmission disequilibrium test[J]. Genet Epidemiol. 2000, 18: 143-156
[114] George V, Tiwari HK, Zhu X, Elston RC. A test of transmission/ disequilibrium for quantitative trait loci in pedigree data, by multiple regression[J]. Am J Hum Genet. 1999, 65: 236- 245.
[115] Knapp M. A note on power approximations for the transmission/ disequilibrium test[J]. Am J Hum Genet. 1999, 64: 1177-1185
[116] Toivonen HT, Onkamo P, Vasko K, Ollikainen V, Sevon P, Mannila H, Herr M, Kere J. Data mining applied to linkage disequilibrium mapping[J]. Am J Hum Genet. 2000, 67: 133-145
[117] Luo ZW, Suhai S. Estimating linkage disequilibrium between a polymorphi c marker locus and a trait locus in natural populations[J]. Genetics. 1999, 151: 359-371
[118] 耿茜，蒋玮莹．人类基因组单体型图计划及其意义[J]．国外医学遗传学分册．2005，28：1-5
[119] Vanden OEJ, Neale BM. Will haplotype maps be useful for finding genes?[J], Mol Psychiaty. 2004, 9: 227-236
[120] Zhang K, Jin L: Haplo Block Finder: haplotype block analyses[J]. Bioinformatics. 2003, 19: 1300-1301
[121] Stephens M, Smith NJ, Donnelly P: A new statistical method for haplotype reconstruction from population data[J]. Am J Hum Genet. 2001, 68: 978-989
[122] Markovic D, Tang X, Guruju M, et al. Association of Angiotensinogen Gene Polymorphisms with Essential Hypertension in African-Americans and Caucasians[J]. Hum Hered. 2005, 60: 89-96
[123] CHEN Li, AO Xue, REN Qun, et al. Linkage Disequilibrium and Haplotype Analysis of Two Single Nucleotide Polymorphisms in STK15 in Chinese[J]. Acta Genetica Sinica. 2005, 32(4): 331-336[1] de Bold AJ, Borenstcin HB, Veress AT, Sonncnberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats[J]. Life Sci. 1981; 28: 89-94
[2] de Bold AJ. Tissue fractionation studies on the relationship between an atrial natriuretic factor and specific atrial granules[J]. Can J Physiol Pharmacol. 1982, 60: 324-330
[3] Flynn TG, de Bold NiL, dc Bold AJ. The amino acid sequence of an atrial pcptidc with potent diuretic and natriurctic properties[J]. Biochem Biophys Rcs Commun. 1983, 117: 859-865
[4] Kangawa K, Matsuo H. Purification and complete amino acid sequence of α-human atrial natriurctic polypcptidc(α-hANP)[J]. Biochem Biophys Rcs Commun. 1984; 118: 131-139
[5] Sudoh T, Kangawa K, Minamino N, et al. A new natriurctic pcptidc in porcine brain[J]. Nature. 1988; 332: 78-81
[6] Minamino N, Aburaya M, Ueda S, et al. The presence of brain natriuretic peptide of 12000 daltons in porcine heart[J]. Biochem Biophys Res Commun. 1988, 155: 740-746
[7] Sudoh T, Minamino N, Kangawa K, et al. C-type natriurctic pcptidc(CNP): a new member of natriurctic peptide family identified in porcine brain[J]. Biochcm biophys Rcs Commun. 1990; 168: 863-870
[8] Minamino N, Makino Y, Tatcyama H, et al. Characterization of immunorcactivc human C-type natriuretic peptide in brain and heart[J]. Biochem biophys Res Commun. 1991; 179: 535-542
[9] Richards AM, Lainchbury JG, Nicholls MG, et al. Dendroaspis natriuretic peptide: endogenous or dubious?[J]. Lancet. 2002; 359: 5-6
[10] 徐丽，陈兰英．利钠肽的结构、受体与生理作用．生物化学与生物 物理进展[J]．2002；29(5)：78
[11] Lang RE, Unger T, Ganten D, et al. Atrial natriuretic peptide: a new??factor in blood pressure control[J]. Hypertension. 1978; 5: 255-271
[12] Oikawa S, Imai M, Ueno A, Tanaka S, et al. Cloning and sequence analysis of cDNA encoding a precursor for human atrial natriuretic polypeptide[J]. Nature. 1984, 309: 724-726
[13] Vuolteenaho O, Arjamaa O, Ling N. Atrial natriuretie polypeptides(ANP): rat atria store high molecular weight precursor but secrete processed peptides of 25- 35 amino acids[J]. Biochem Biophys Res Commun. 1985, 129: 82-88
[14] Hall C, Rouleau JL, Moye L, et al. N—termianal proatrial natriuretic factor an independent predictor of long-term prognosis after myocardial infarction[J]. Circulation. 1994, 89(5): 1934
[15] Hunt PJ, Riehards AM, Nieholls MG, et al. Immunoreaetive Aminoterminal probrain natriuretic peptide(NT-PROBNP): a new marker of cardiac impairment[J]. Clin Endoerinol. 1997, 47: 287-296.
[16] Biondo AW, Liu ZL. Genomic sequence and cardiac expression of atrial natriuretic peptide in cats[J]: AmJ Vet Res. 2002, 63(2): 236-240.
[17] Baxter GF. The natriuretie peptides: An introduction[J]. Basic Res Cardiol. 2004, 99: 71-75
[18] Lerman A, Gibbons RJ, Rodeheffer RJ, et al. Circulating N-termianal atrial natriuretic peptide as a marker for symptomless left ventricular dysfunction[J]. Lancet. 1993, 341(8853): 1105-1109
[19] Kettunen RVJ, Leppaluto J, Jounela A, et al. Plasma N-termianal atrial natriuretic peptide in acute myocardial infarction[J]. Am Heart J. 1994, 127(6): 1449
[20] 温绍君，张维君，王金城，等．心包心钠素的基因表达[J]．中华心血管病杂志，1999；27(5)：345
[21] 邵春来，洪小苏．脑利钠肽与心血管疾病的研究进展[J]．心血管病学进展．2005，26(1)：36-40
[22] 刘晓柳，李光千．心房利钠肽与心血管系统疾病[J]．国外医学临??床生物化学与检验分册. 2003,24(3):135-136
[23] Sahai A, Ganguly PK. Atrial natriuretic peptide: pathophysio logical considerations [J]. Indian Journal of Physiology and Pharmacology. 1992,36:314
[24] Ruskoaho H. Atrial natriuretic pep tide: synthesis, release, and metabolism[J]. Pharmacological Reviews. 1992,44:479-602
[25] Ruskoaho H. Atrial natriuretic peptide: synthesis, release, and metabolism[J]. Pharmacol Rev. 1992,44:479-602
[26] Richards AM. The natriuretic peptides in heart failure[J]. Basic Res Cardiol. 2004,99(2):94-100
[27] Lang RE, Tholken H, Ganten D, et al. Atrial natriuretic factor-a circulating hormone stimulated by volume loading[J]. Nature. 1985,314:264-266
[28] Toth M, Vuorinen KH, Vuolteenaho O, et al. Hypoxia stimulates release ofANPand BNP from perfused rat ventricular myocardium [J]. Am J Physiol. 1994, 266:H1572-H1580
[29] Nakanishi K, Tajima F. Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats[J]. Virchows Arch. 2001,439(6): 808-817
[30] Kyriakides ZS, Markianos M, Michalis L, et al. Brain natriuretic peptide increases acutely and much more prominently than atrial natriuretic peptide during coronary angioplasty[J]. Clin Cardiol. 2000,23:285-288
[31] Schiebinger RT, GornezSanchez CE. Endothelin, a potent stimulus of atrial natriuretic peptide secretion by superfused rat atrial and its dependency on calcium [J]. Endocrinology. 1990,27:119
[32] Leskinen H, Vuolteenaho O , Ruskoaho H. Combined inhibition of endothelin and angiotensin II receptors blocks volume load induced cardiac hormone release [J]. Circ Res. 1997,80:114-123
[33] Focacio A, Volpe M, Ambrosio G, t al. Angiotensin Ⅱ directly stimulates release of atrial natriuretic factor in isolated rabbit hearts[J]. Circulation. 1993, 87: 192-198
[34] 万光霞，邬玉芳．原发性高血压患者血浆心钠素水平探讨[J]．标记免疫分析与临床．2002，9(4)：251-252
[35] 童晓明，吕承忠(综述)，侯家声审校．利钠肽与缺血性心脏病[J]．心血管病学进展．2000，21(6)：343-346
[36] 黄陈军，朱文玲，陈连风，等．N-末端心房利钠肽和脑利钠肽对充血性心力衰竭的诊断意义[J]．中华心血管病杂志．2003，31(6)：405-407
[37] Sayama H, Nakamura Y, Saito N, et al. Why is the concentration of plasma brain natriuretic peptide in elderly inpatients greater than normal?[J]. Coron Artery Dis. 1999, 10: 537-540
[38] 杨俊娟，唐朝枢，张钧华．C型利钠利尿肽与心血管疾病[J]．生理科学进展．2001，32(3)：257-259
[39] 周思翔，华慧，王正荣．心房肽的研究进展[J]．西部医学．2003，1：361-363
[40] Weidmann P, hasler L, Gnadinger MP, et al. Blood levels and renal effects of atrial natriuretic peptide in normal man[J]. J Clin Invest. 1986, 77: 734-742
[41] Loutzenhiser R, Hayashi K, Epstein M. Atrial natriuretic peptide reverses afferent arteriolar vasoconstriction and potentiates efferent arteriolar vasoconstriction in the isolated perfused rat kidney[J]. Journal of Pharmacology & Experimental Therapeutics. 1988, 246(2): 522-588
[42] Huang CL, Lewicki J, Johnson LK, et al. Renal mechanism of action of rat atrial natriuretic factor[J]. J Clin invest. 1988, 75: 769-773
[43] 李素琴，符云峰．心房肽与心血管疾病[J]．医学综述．1996，2(6)：273-275
[44] Winquist RJ, Faison EP, Waldman SA, et al. Atrial natriuretic factorelicits an endothelium independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle[J]. Proc Natl Acad Sci.USA.1984, 81:7661-7664
[45] Meisheir KD. Synthetic atrial peptide inhibits intracellular calcium release in smooth muscle[J]. Am J physiol.1986,250:171-174
[46] Wijeyaratne CN, Moult PJA. The effect of a human atrial natriuretic peptide on plasma volume and vascular permeability in normotensive subjects[J]. Journal of Clinical Endocrinology and Metabolism. 1993, 76: 343-346
[47] Kinugawa T, Endo A, Kato M, et al. Responses of plasma catecholamines, renin-angiotensin-aldosterone system and atrial natriuretic peptide to exercise in patients with essential hypertension[J]. Cardiology. 1997,88: 238-245
[48] Gutkowska J, Antunes RJ, McCann SM.Atrial natriuretic peptide in brain and pituitary gland[J]. Physiol Res. 1997,77(2):465
[49] Doczi TP, joo FL, Balas I, et al. Atrial natriuretic peptide attenuates brain edema accompanying subarachnoid hemorrsge[J]. Acta Neurochir.1995,13(2):87
[50] Howard GH. Mechanism of natriuretic peptide induced growth inhibition of vascular smooth muscle cells[J]. Cardiovas Res.l997,35:158
[51] Barber MN, Gaspari TA, Kairuz EM, et al. Atrial natriuretic peptide preserves endothelial function during Intimal Hyperplasia[J]. J Vasc Res. 2005,42:101-110
[52] Abeli TJ, Richards AM, Ikram H, et al. Atrial natriuretic factor inhibits proliferation of vascular smooth muscle cells stimulated by platelet-derived growth factor[J]. Biochem Biophys Res Common . 1997,17:731-736.
[53] Ikeda M, Kohno M, Yokohawa K, et al. Natriuretic peptide family as a novel antimigration factor of vascular smooth muscle[J].Arterioscler Thromb Vasc Bio1. 1997, 17: 731-736
[54] Matsue H. Atrial natriuretic peptide protein inhibit intimal thickening after vascular injury[J]. Ann NY Acad Sci. 1997, 81(1): 45
[55] 邱洪棋，李进攘，李跃辉，等．高血压患者血浆内皮素．心房肽的变化及缓释维拉帕米的影响[J]．高血压杂志．1996，4(3)：219
[56] 朱守成，李祥峰．心钠素的临床研究近况[J]．中国误诊学杂志．2003，3(7)：1001-1002
[57] 李付远，梅益斌，童朋军，等．原发性高血压患者血清利钠肽水平的变化[J]．放射免疫学杂志．2005，18：13-16
[58] Melander 0, Frandsen E. Plasma ProANP(1-30)reflects salt sensitivity in subjecs with heredity for hypertension[J]. Hypertension. 2002, 39(5): 996-999
[59] Nishikimi T, Yoshihara F, Morimoto A, et al. Relationship between left ventricular geometry and natriuretic Peptide levels in essential hypertension[J]. Hypertension. 1996, 28(1): 22-30
[60] Nakayama T, Soma M, Takahashi Y, et al. Functional deletion mutation of the 5'-flanking region of type a human natriuretic peptide receptor gene and its association with essential hypertension and left ventricular hypertrophy in the Japanese[J]. Circulation Research. 2000, 86(8): 841-845
[61] 邵春来，洪小苏，陈建昌，等．原发性高血压患者血浆利钠肽水平的变化[J]．苏州大学学报(医学版)．2005，25(1)：101-103
[62] 乔延国，张开，王英．高血压病左室肥厚患者血浆脑利钠肽与心房利钠肽的变化[J]．高血压杂志．2005，13(7)：419-421
[63] 季乃军，应秀华，梅益斌，等．原发性高血压患者血清部分血管活性肽的测定及其临床意义[J]．河北医学．2001，7：961-963
[64] Baxter, G. F. Natriuretie peptides and myocardial ischaemia[J]. Basic Res Cardiol. 2004, 99: 90-93
[65] Kuhn M, Roltwick R, Baba HA, et al. Progressive cardiac hypertrophy and dysfunction in atrial natriuretie peptide(GC-A)??deficient mice[J]. Heart. 2002, 87: 368-374
[66] Franco-Saenz R, Somani P, Mulrow PJ. Effect of atrial natriuretic peptide(8-33-metAN P)in patients with hypertension[J]. American Journal of Hypertension. 1992, 5: 266-275
[67] Lcvin ER, Gardner DG, Sasmon WK, et al. Natriurctic peptidc[J]. Engl J Med. 1998, 339: 321-327
[68] Chcung BM, Chir MBB, Kumana CR, et al. Natriurctic peptides-relevance incardiovascular disease[J]. JAMA. 1998, 280(23): 1983-1984
[69] 丁金凤，秦阳君，孙巨忠，等．自发性高血压大鼠肌肉注射心钠素基因的降压作用[J]．中国循环杂志．1997，12(4)：245-248
[70] 张培荣，王宇航，黄彦生．N-心钠素在无症状性心力衰竭中的诊断价值[J]．临床荟萃．2001，16：244-246
[71] 许波宁，胡大一，贾三庆，等．冠状动脉粥样硬化性心脏病患者血浆心钠素水平与早期心功能障碍关系的观测[J]．中国危重病急救医学．1999，11(1)：44
[72] Hall C, Kjekshus J, Eneroch P, et al. The plasma concentration of N-terminal proatrial natriuretic factor ANF(1298) is related toprognosis in severe heart failure[J]. Clin Cardiol. 1994, 17: 191-195
[73] 徐成斌，王炳银，王静毅，等．充血性心力衰竭患者心钠素研究[J]．中华内科杂志．1992，31(1)：37
[74] 李尚俭，陈新义，田文华，等．慢性心力衰竭患者血浆肾上腺皮质激素及心钠素的含量及分析[J]．心血管康复医学杂志．2005，14：213-215
[75] 孙世忠，杨事达，翁亚贤，等．慢性心力衰竭患者血浆心房利钠肽水平的检测及其与发病的相关性分析[J]．现代检验医学杂志．2005，20：24-26
[76] Malaia LT, Volnenko NB, Gorb IuG. Several aspects of the patho-genesis of chronic circulatory failure in ischemic heart??disease: role of atrial natriuretm peptide[J]. Cardiology. 1990, 30(9): 28
[77] Dickstein K, Abrahamsen S, Aarsland T. Plasma n-terminal atrial natriuretic peptide predicts hospitalisation in patients with heart failure[J]. Scandinavian Cardiovascular Journal. 1998, 32: 361-364
[78] 云璐，黄健全，刘俊田．心钠素对心血管系统的作用和调节[J]．遵义医学院学报．2002，25：276-278
[79] Kelly R, Struthers AD. Are natriuretic peptides clinically useful as markers of heart failure?[J]. Ann Clin Biochem. 2001, 38: 94-102
[80] Tsutamoto T, Wada A, Maeda K, et al. Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure. Circulation[J]. 1997, 96(2): 509-516
[81] Tsutamoto T, Kanamori T, Morigami N, et al. Possibility of downregulation, of atrial natriuretic peptide receptor coupled to guanylate cyclase in peripheral vascular beds of patients with chronic severe heart failure[J]. Circulation. 1993, 87(1): 70-75
[82] Denofrio D. Natriuretic peptide for treatment of congestive heart failure[J]. Am Heart J. 1999, 138: 597-598
[83] 王兴祥，陈君柱，程龙献，等．心力衰竭患者血清钠对血浆肾素、醛固酮和心钠素的影响[J]．中国综合临床．2004，20(1)：10-12
[84] Macho P, Vatner SF. Effect of nitroglycerin and nitroprusside on large and small coronary vessels in conscious dog[J]. Circulation. 1981, 64: 1101-1107
[85] 刘全，赵慧颖，程莉，等．心钠素对犬冠状动脉循环的调节作用[J]．吉林大学学报(医学版)．2003，29：789-791
[86] Marumoto K, Hamada M, Hiwada K, et al. Increased secretion of atrial and brain natriuretie peptides during acute myocardial ischaem ia induced by dynam ie exercise in patients with angina pectoris[J]. Clin Sci. 1995, 88: 551-556
[87] Kikuta K, Yasue H, Yoshimure M, et al. Increased plasma level of??B-type natriuretic peptide in patientsw ith unstable angina[J]. Am Heart J. 1996, 131: 101-107
[88] Rouleau JL, Packer M, Moye L, et al. Prognostic value of neurohumoral activation in patients with an acute myocardial infaction[J]. Journal of American College of Cardiology. 1994, 24: 583-591
[89] 彭建军，吴场，胡大一，等．急性心肌梗死患者急诊冠状动脉介入治疗前后血浆心钠素的动态变化及其预后意义[J]．中国医药导刊．2004，6(5)：340-342
[90] Stein BC, L evin RI. Natriuretic peptides: Physiology, therapeutic po tential, and risk stratification in ischemic heart disease[J]. Am Heart J. 1998, 135: 914-923
[91] 汤哗华，黄高忠，吴宗贵．急性冠脉综合征患者血利钠肽水平变化及其意义[J]．医学综述．2005，11(5)：392-394
[92] The CONSENSUS(Cooperative North Scandina vian Enalapril Survival Study)I Study Group(Swedberg). Early Enalapril after Myocardial Infarction[J]. N Engl J Med. 1992, 327: 678-684
[93] Hall C, Cannon CP, Forman S, et al. Prognostic value of N-terminal pro-atrial natriuretic factor plasma levels measured with in the first 12 hours after myocardial infarction[J]. J Am Co Ⅱ Cardial, 1995, 26: 145-242
[94] The SAVE(Survival and Ventricular Enlargement)Study Group. Effect of Captopril after Myocardial Infarction[J]. N Engl J Med. 1992, 327(10): 699-677
[95] Omland T, Bonarjee WS, Nilsen DWT, et al. Prognostic significance of N-terminal pro-atrial natriuretic factor in acute myocardial infarction: comparison with atrial natriuretic factor and clinical evaluation[J]. Br Heart J. 1993, 70: 409-414
[96] Bonarjee WS, Omland T, Nilsen DWT, et al. Plasma proatrial natriuretic factor concentration after myocardial infarction: relation??to indices of cardiac and renal function[J]. Br Heart J. 1995, 73: 511-516
[97] Herrmann HC, Rosen AD, Davis CA. Cardiovascular effect of intracoronary atrial natriuretic peptide administration in man[J]. Am Heart J. 1990, 120: 308-315
[98] Kosuge M, Miyajima E, Kimura K, et al. Efficacy of atrial natriuretic peptide is a vasodilator for the treat[J]. Circulation. 1996, 94: 82-89
[99] 夏小杰，昝沁，杨俊芬，等．心房颤动患者血浆心钠素浓度变化的研究[J]．放射免疫学杂志．2004，17：32-34
[100] Wozakowska-Kaplon B, Opolski G. Concomitant recovery of atrial mechanical and endocrine function after cardioversion in patient with persistent atrial fibrillation[J]. J Am Coil Cardiol. 2003, 41(10): 1716
[101] 华琦，汪家瑞，师树英，等．心脏结构、心内血流及心功能与循环心钠素、肾素-血管紧张素系统[J]．中华内科杂志．1994，33(3)：165-167
[102] Rossi A, Burnett jc, Leman A, et al. Natriuretic peptide levels in atrial fibrillation[J]. J Am Coll Cardiol. 2000, 35(5): 1256-1261
[103] Globis S, Frank H, Pacher B, et al. Atrial natriuretic peptide release is more dependent on atrial filling volume than on filling pressure in chronic congestive heart failure[J]. Am Heart J. 1998, 135: 592
[104] Fumiki Y, Toshio N, Yoshikado S, et al. Plasma atrial natriuretic pep tide concentration inversely correlates with left atrial collagen volume fraction in patients with atrial fibrillation[J]. JACC. 2002, 39: 288-294
[105] 王卫明，孙建辉，许国锋，等．心房颤动患者血浆心钠素C反应蛋白浓度测定及其意义[J]．江苏大学学报(医学版)．2005，15(3)：244-246
[106] 孙永波，李滨，孙艳玲．钠尿肽系统与原发性高血压及左心室重??塑研究的某些新进展[J]．临床荟萃．2004，19：294-295
[107] Lin KF, Chao J, Chao L. A trial natriuretie peptide gene delivery reduces stroke-induced mortality rate in dah l salt- sensitive rats[J]. Hypertension. 1999, 33, 219-224
[108] Hideyuki Murakami, Katsutishi Yayama, Julie Chao et al. Atrial natriuretic peptide gene delivery attenuates gentamycin -induced nephro toxicity in rats[J]. Nephrol Dial Transplant. 1999, 14: 1376-1384
[109] Li Guo Chert, Zheng Rong Wang, Yi Qu. In vitro evaluation of AN P eDNA transfection cells encapsulated in PCL-tubes and its circadian expression[J]. Space Med Med Eng. 2003, 16(3): 179-183