The association between the angiotensin-converting enzyme-2 gene and blood pressure in a cohort study of adolescents

BMC Medical Genetics

Gilles Paradis¹  Johanne Tremblay³  Pavel Hamet³  Louise Pilote²  Aurélie Labbe¹  Marie-Hélène Roy-Gagnon⁶  Jennifer O’Loughlin⁴  Lisa Kakinami¹  Lucile Malard⁵ 

[1] Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, QC, Canada;Department of Medicine, McGill University and McGill University Health Center, Montréal, QC, Canada;Department of Medicine, Centre de recherche du CHUM, Université de Montréal, Montréal, QC, Canada;CRCHUM, Département de médecine sociale et préventive, Université de Montréal, Montréal, QC, Canada;Institut de Santé Publique d’Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen, Bordeaux, France;Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada

关键词: Cohort study;    Adolescent;    Angiotensin-Converting Enzyme-2;    Blood pressure;   

Others  :  1122582
DOI  :  10.1186/1471-2350-14-117

 received in 2013-01-17, accepted in 2013-10-30,  发布年份 2013

【 摘 要 】

Background

The Angiotensin-Converting Enzyme-2 (ACE2) gene, located on chromosome X, is believed to be implicated in blood pressure regulation. However the few studies that have examined this association have yielded mixed results. The objective of this study was to assess the association between tag single nucleotide polymorphisms (SNPs) in the angiotensin-converting enzyme-2 gene with blood pressure and blood pressure change in adolescents.

Methods

Participants in the Nicotine Dependence in Teens (NDIT) cohort study with blood or saliva samples and at least 3 blood pressure measurements over 5 years were included in the analytic sample (n = 555). Linear growth curve models stratified on sex and ethnicity were used to assess the association between four tag SNPs in the ACE2 gene and systolic (SBP) and diastolic blood pressure (DBP), and blood pressure change.

Results

In males of European descent, rs2074192 and rs233575 were significantly associated with SBP and DBP, and rs2158083 was associated with SBP. In French Canadian males, rs233575 and rs2158083 were significantly associated with DBP. Among females of European descent, rs2074192, rs233575, and rs2158083 were significantly associated with change in SBP over 5 years.

Conclusions

This is the first study to assess the association between the ACE2 gene with blood pressure and blood pressure change in a cohort of adolescents. Results indicate that several ACE2 gene SNPs are associated with blood pressure or blood pressure change in persons of European descent. However the therapeutic potential of these SNPs should be explored.

【 授权许可】

   
2013 Malard et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Lawes CMM, Hoorn SV, Rodgers A: Global burden of blood-pressure-related disease, 2001. Lancet 2008, 371(9623):1513-1518.
• [2]Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J: Global burden of hypertension: analysis of worldwide data. Lancet 2005, 365(9455):217-223.
• [3]Van Rijn MJE, Schut AF, Aulchenko Y, Deinum J, Sayed-Tabatabaei FA, Yazdanpanah M, Isaacs A, Axenovich TI, Zorkoltseva IV, Zillikens MC, et al.: Heritability of blood pressure traits and the genetic contribution to blood pressure variance explained by four blood-pressure-related genes. J Hypertens 2007, 25(3):565-570.
• [4]Pilia G, Chen W-M, Scuteri A, Orrú M, Albai G, Dei M, Lai S, Usala G, Lai M, Loi P, et al.: Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet 2006, 2(8):e132.
• [5]Snieder H, Harshfield GA, Treiber FA: Heritability of blood pressure and hemodynamics in African- and European-American youth. Hypertension 2003, 41(6):1196-1201.
• [6]Levy D, Larson M, Benjamin E, Newton-Cheh C, Wang T, Hwang S-J, Vasan R, Mitchell G: Framingham heart study 100K project: genome-wide associations for blood pressure and arterial stiffness. BMC Med Genet 2007, 8(Suppl 1):S3. BioMed Central Full Text
• [7]Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ: A human homolog of angiotensin-converting enzyme. J Biol Chem 2000, 275(43):33238-33243.
• [8]Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, et al.: A novel angiotensin-converting enzyme related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res 2000, 87(5):e1-e9.
• [9]Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-dos-Santos AJ, da Costa J, Zhang L, Pei Y, et al.: Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 2002, 417(6891):822-828.
• [10]Danilczyk U, Penninger JM: Angiotensin-converting enzyme II in the heart and the kidney. Circ Res 2006, 98(4):463-471.
• [11]Huang W, Yang W, Wang Y, Zhao Q, Gu D, Chen R: Association study of angiotensin-converting enzyme 2 gene (ACE2) polymorphisms and essential hypertension in northern Han Chinese. J Hum Hypertens 2006, 20(12):968-971.
• [12]Gurley SB, Allred A, Le TH, Griffiths R, Mao L, Philip N, Haystead TA, Donoghue M, Breitbart RE, Acton SL, et al.: Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J Clin Invest 2006, 116(8):2218-2225.
• [13]Benjafield AV, Wang WYS, Morris BJ: No association of angiotensin-converting enzyme 2 gene (ACE2) polymorphisms with essential hypertension. Am J Hypertens 2004, 17(7):624-628.
• [14]Lieb W, Graf J, Götz A, König I, Mayer B, Fischer M, Stritzke J, Hengstenberg C, Holmer S, Döring A, et al.: Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men. Results of the MONICA Augsburg echocardiographic substudy. J Mol Med (Berl) 2006, 84(1):88-96.
• [15]Fan X, Wang Y, Sun K, Zhang W, Yang X, Wang S, Zhen Y, Wang J, Li W, Han Y, et al.: Polymorphisms of ACE2 gene are associated with essential hypertension and antihypertensive effects of Captopril in women. Clin Pharmacol Ther 2007, 82(2):187-196.
• [16]Yi L, Gu YH, Wang XL, An LZ, Xie XD, Shao W, Ma LY, Fang JR, An YD, Wang F, et al.: Association of ACE, ACE2 and UTS2 polymorphisms with essential hypertension in Han and Dongxiang populations from North-western China. J Int Med Res 2006, 34(3):272-283.
• [17]O’Loughlin J, Karp I, Koulis T, Paradis G, Difranza J: Determinants of first puff and daily cigarette smoking in adolescents. Am J Epidemiol 2009, 170(5):585-597.
• [18]O’Loughlin J, Karp I, Henderson M, Gray-Donald K: Does cigarette use influence adiposity or height in adolescence? Ann Epidemiol 2008, 18(5):395-402.
• [19]Maximova K, O’Loughlin J, Paradis G, Hanley JA, Lynch J: Declines in physical activity and higher systolic blood pressure in adolescence. Am J Epidemiol 2009, 170(9):1084-1094.
• [20]Centers for Disease Control and Prevention: A SAS program for the CDC growth charts. Available at http://www.cdc.gov/nccdphp/dnpao/growthcharts/resources/sas.htm webcite
• [21]de Bakker PIW, Yelensky R, Pe’er I, Gabriel SB, Daly MJ, Altshuler D: Efficiency and power in genetic association studies. Nat Genet 2005, 37(11):1217-1223.
• [22]Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21(2):263-265.
• [23]Shankar RR, Eckert GJ, Saha C, Tu W, Pratt JH: The change in blood pressure during pubertal growth. J Clin Endocrinol Metab 2005, 90(1):163-167.
• [24]Maximova K, O’Loughlin J, Paradis G, Hanley JA, Lynch J: Changes in anthropometric characteristics and blood pressure during adolescence. Epidemiology 2010, 21(3):324-331.
• [25]Fossella J, Sommer T, Fan J, Wu Y, Swanson JM, Pfaff DW, Posner MI: Assessing the molecular genetics of attention networks. BMC Neurosci 2002, 3:14. BioMed Central Full Text
• [26]Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K: dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 2001, 29(1):308-311.
• [27]Cook NR, Ware JH: Design and analysis methods for longitudinal research. Annu Rev Public Health 1983, 4:1-23.
• [28]Zhao Q, Hixson JE, Rao DC, Gu D, Jaquish CE, Rice T, Shimmin LC, Chen J, Cao J, Kelly TN, et al.: Genetic variants in the apelin system and blood pressure responses to dietary sodium interventions: a family-based association study. J Hypertens 2010, 28(4):756-763.
• [29]Zhu M, Zhao S: Candidate gene identification approach: progress and challenges. Int J Biol Sci 2007, 3(7):420-427.
• [30]Jorgensen TJ, Ruczinski I, Kessing B, Smith MW, Shugart YY, Alberg AJ: Hypothesis-driven candidate gene association studies: practical design and analytical considerations. Am J Epidemiol 2009, 170(8):986-993.
• [31]Clayton D: Testing for association on the X chromosome. Biostatistics (Oxford, England) 2008, 9(4):593-600.
• [32]Clayton DG: Sex chromosomes and genetic association studies. Gen Med 2009, 1(11):110.
• [33]Hickey PF, Bahlo M: X chromosome association testing in genome wide association studies. Gen Epidemiol 2011, 35(7):664-670.
• [34]Brown MJ: Hypertension and ethnic group. BMJ 2006, 332(7545):833-836.