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01-08-2015 | Translational Neurosciences - Original Article

Angiotensin-converting enzyme gene insertion-deletion polymorphism is a risk marker for Alzheimer’s disease in a Chinese population: a meta-analysis of case–control studies

Authors: Ye Yuan, Jin-hua Piao, Ke Ma, Na Lu

Published in: Journal of Neural Transmission | Issue 8/2015

Abstract

It has long been known that the polymorphisms of angiotensin-converting enzyme gene (ACE) are associated to increase risk of Alzheimer’s disease (AD) in Chinese population. However, consistent results were not obtained among studies. This study is aimed to clarify the association between ACE insertion (I)/deletion (D) polymorphism (rs1799752) and AD. Literatures were searched from PubMed, Embase, Cochrane Library, CNKI, Wanfang and VIP databases without language restrictions. Eleven separate studies were suitable for the inclusion criterion. The selected studies contained 2,763 Chinese participants, including 1,383 in AD group and 1,380 controls. Pooled odds ratios (ORs) were calculated to assess the association between ACE I/D polymorphism and AD. Our case–control data indicated that ACE insertion is a risk allele in all genetic models: additive model (I vs. D: OR = 1.32, 95 % CI 1.07–1.62, P = 0.008), dominant model (II + ID vs. DD: OR = 1.61, 95 % CI 1.08–2.41, P = 0.02) and recessive model (II vs. ID + DD: OR = 1.39, 95 % CI 1.07–1.81, P = 0.01). Heterogeneity between studies was significant (P < 0.10) but not in stratification defined by the selection of controls (P > 0.10). After stratification according to the selection of controls, the carrier of ACE I allele remained a high risk for AD in population-based samples subgroup (I vs. D: P = 0.008, OR = 1.32, 95 % CI 1.07–1.61, P _{heterogeneity} = 0.47, I ² = 0 %). Our study provided solid evidence suggesting that ACE gene I/D polymorphism is a genetic risk factor for AD in Chinese population.

Almeida SS, Barros CC, Moraes MR, Russo FJ, Haro AS, Rosa TS, Alves MF, Pesquero JB, Carmona AK, Bacurau RF, Araujo RC (2010) Plasma Kallikrein and Angiotensin I-converting enzyme N- and C-terminal domain activities are modulated by the insertion/deletion polymorphism. Neuropeptides 44(2):139–143. doi:10.1016/j.npep.2009.12.003 PubMedCrossRef

Alvarez R, Alvarez V, Lahoz CH, Martinez C, Pena J, Sanchez JM, Guisasola LM, Salas-Puig J, Moris G, Vidal JA, Ribacoba R, Menes BB, Uria D, Coto E (1999) Angiotensin converting enzyme and endothelial nitric oxide synthase DNA polymorphisms and late onset Alzheimer’s disease. J Neurol Neurosurg Psychiatry 67(6):733–736PubMedCentralPubMedCrossRef

Blacker D, Haines JL, Rodes L, Terwedow H, Go RC, Harrell LE, Perry RT, Bassett SS, Chase G, Meyers D, Albert MS, Tanzi R (1997) ApoE-4 and age at onset of Alzheimer’s disease: the NIMH genetics initiative. Neurology 48(1):139–147PubMedCrossRef

Brunden KR, Trojanowski JQ, Lee VM (2009) Advances in tau-focused drug discovery for Alzheimer’s disease and related tauopathies. Nat Rev Drug Discov 8(10):783–793. doi:10.1038/nrd2959 PubMedCentralPubMedCrossRef

Carbonell J, Allen R, Kalsi G, McQuillin A, Livingston G, Katona C, Walker Z, Katz A, Rands G, Stevens T, Crossan I, Curtis D, Gurling H (2003) Variation in the DCP1 gene, encoding the angiotensin converting enzyme ACE, is not associated with increased susceptibility to Alzheimer’s disease. Psychiatr Genet 13(1):47–50. doi:10.1097/01.ypg.0000054711.85338.5c PubMedCrossRef

Chapman J, Wang N, Treves TA, Korczyn AD, Bornstein NM (1998) ACE, MTHFR, factor V Leiden, and APOE polymorphisms in patients with vascular and Alzheimer’s dementia. Stroke 29(7):1401–1404PubMedCrossRef

Cheng CY, Hong CJ, Liu HC, Liu TY, Tsai SJ (2002) Study of the association between Alzheimer’s disease and angiotensin-converting enzyme gene polymorphism using DNA from lymphocytes. Eur Neurol 47(1):26–29PubMedCrossRef

DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188PubMedCrossRef

Elkins JS, Douglas VC, Johnston SC (2004) Alzheimer disease risk and genetic variation in ACE: a meta-analysis. Neurology 62(3):363–368PubMedCrossRef

Erdos EG, Skidgel RA (1987) The angiotensin I-converting enzyme. Lab Invest 56(4):345–348PubMed

Han B, Zhang SL (2006) Association of apoE gene, A2 M gene and ACE gene polymorphism with Alzheimer’s disease. J Shanxi Univ

He M, Ohrui T, Maruyama M, Tomita N, Nakayama K, Higuchi M, Furukawa K, Arai H (2006) ACE activity in CSF of patients with mild cognitive impairment and Alzheimer disease. Neurology 67(7):1309–1310. doi:10.1212/01.wnl.0000238102.04582.ec PubMedCrossRef

Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. doi:10.1002/sim.1186 PubMedCrossRef

Higgins J, Thompson S, Deeks J, Altman D (2002) Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice. J Health Serv Res Policy 7(1):51–61PubMedCrossRef

Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi:10.1136/bmj.327.7414.557 PubMedCentralPubMedCrossRef

Hu J, Igarashi A, Kamata M, Nakagawa H (2001) Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A beta); retards A beta aggregation, deposition, fibril formation; and inhibits cytotoxicity. J Biol Chem 276(51):47863–47868. doi:10.1074/jbc.M104068200 PubMed

Isbir T, Agachan B, Yilmaz H, Aydin M, Kara I, Eker D, Eker E (2001) Interaction between apolipoprotein-E and angiotensin-converting enzyme genotype in Alzheimer’s disease. Am J Alzheimers Dis Other Demen 16(4):205–210PubMedCrossRef

Kehoe PG, Russ C, McIlory S, Williams H, Holmans P, Holmes C, Liolitsa D, Vahidassr D, Powell J, McGleenon B, Liddell M, Plomin R, Dynan K, Williams N, Neal J, Cairns NJ, Wilcock G, Passmore P, Lovestone S, Williams J, Owen MJ (1999) Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease. Nat Genet 21(1):71–72. doi:10.1038/5009 PubMedCrossRef

Kolsch H, Jessen F, Freymann N, Kreis M, Hentschel F, Maier W, Heun R (2005) ACE I/D polymorphism is a risk factor of Alzheimer’s disease but not of vascular dementia. Neurosci Lett 377(1):37–39. doi:10.1016/j.neulet.2004.11.062 PubMedCrossRef

Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127(9):820–826PubMedCrossRef

Lehmann DJ, Cortina-Borja M, Warden DR, Smith AD, Sleegers K, Prince JA, van Duijn CM, Kehoe PG (2005) Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer’s disease. Am J Epidemiol 162(4):305–317. doi:10.1093/aje/kwi202 PubMedCrossRef

Li S, Zheng LB, Jin F (2003) Late-onset alzheimer’s disease susceptibility genes. J Tianjing Teach Train Univ 2003

Liu M, Zhang YD (2004) Association of Serum Angiotensin converting enzyme activity and Angiotensin converting enzyme Gene Polymorphism with Senile Dementia. J Nanjing Med Univ

Liu M, Zhang YD, Zhao KR, Liu Y (2007) Association of angiotensin converting enzyme activity and angiotensin converting enzyme gene polymorphism with vascular dementia and Alzheimer’s disease. Chin J Pract Intern Med 27(13):1028–1030

Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748PubMed

Martin LJ, Pardo CA, Cork LC, Price DL (1994) Synaptic pathology and glial responses to neuronal injury precede the formation of senile plaques and amyloid deposits in the aging cerebral cortex. Am J Pathol 145(6):1358–1381PubMedCentralPubMed

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34(7):939–944PubMedCrossRef

Monastero R, Caldarella R, Mannino M, Cefalu AB, Lopez G, Noto D, Camarda C, Camarda LK, Notarbartolo A, Averna MR, Camarda R (2002) Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer’s disease. Neurosci Lett 335(2):147–149PubMedCrossRef

Munafo MR, Flint J (2004) Meta-analysis of genetic association studies. Trends Genet TIG 20(9):439–444. doi:10.1016/j.tig.2004.06.014 PubMedCrossRef

Ning M, Yang Y, Zhang Z, Chen Z, Zhao T, Zhang D, Zhou D, Xu J, Liu Z, Wang Y, Liu Y, Zhao X, Li W, Li S, He L (2010) Amyloid-beta-related genes SORL1 and ACE are genetically associated with risk for late-onset Alzheimer Disease in the Chinese population. Alzheimer Dis Assoc Disord 24(4):390–396. doi:10.1097/WAD.0b013e3181e6a575 PubMedCrossRef

Palumbo B, Cadini D, Nocentini G, Filipponi E, Fravolini ML, Senin U (1999) Angiotensin converting enzyme deletion allele in different kinds of dementia disorders. Neurosci Lett 267(2):97–100PubMedCrossRef

Perry RT, Collins JS, Harrell LE, Acton RT, Go RC (2001) Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age-matched controls. Am J Med Genet 105(4):332–342PubMedCrossRef

Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86(4):1343–1346. doi:10.1172/JCI114844 PubMedCentralPubMedCrossRef

Roses AD (1996) The Alzheimer diseases. Curr Opin Neurobiol 6(5):644–650PubMedCrossRef

Rubinsztein DC, Easton DF (1999) Apolipoprotein E genetic variation and Alzheimer’s disease. a meta-analysis. Dement Geriatr Cogn Disord 10(3):199–209 (17120)PubMedCrossRef

Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ et al (1993) Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 43(8):1467–1472PubMedCrossRef

Savaskan E, Hock C, Olivieri G, Bruttel S, Rosenberg C, Hulette C, Muller-Spahn F (2001) Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer’s dementia. Neurobiol Aging 22(4):541–546PubMedCrossRef

Scacchi R, De Bernardini L, Mantuano E, Vilardo T, Donini LM, Ruggeri M, Gemma AT, Pascone R, Corbo RM (1998) DNA polymorphisms of apolipoprotein B and angiotensin I-converting enzyme genes and relationships with lipid levels in Italian patients with vascular dementia or Alzheimer’s disease. Dement Geriatr Cogn Disord 9(4):186–190PubMedCrossRef

Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24(9):1291–1306. doi:10.1002/sim.2010 PubMedCrossRef

Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F (1992) Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 51(1):197–205PubMedCentralPubMed

Wang B, Jin F, Yang Z, Lu Z, Kan R, Li S, Zheng C, Wang L (2006) The insertion polymorphism in angiotensin-converting enzyme gene associated with the APOE epsilon 4 allele increases the risk of late-onset Alzheimer disease. J Mol Neurosci : MN 30(3):267–271. doi:10.1385/JMN:30:3:267 PubMedCrossRef

Woolf B (1955) On estimating the relation between blood group and disease. Ann Hum Genet 19(4):251–253PubMedCrossRef

Wu CS, Zhou DF, Guan ZQ, Fan JH, Qiao YL (2002) The association between angiotensin I converting enzyme gene polymorphism and Chinese late onset Alzheimer Disease. Chin J Med Gene 19(5):401–404

Yang JD, Feng G, Zhang J, Lin ZX, Shen T, Breen G, St Clair D, He L (2000) Association between angiotensin-converting enzyme gene and late onset Alzheimer’s disease in Han chinese. Neurosci Lett 295(1–2):41–44PubMedCrossRef

Yang YH, Lai CL, Tyan YC, Chou MC, Wang LC, Yang MH, Liu CK (2011) Angiotensin-converting enzyme gene and plasma protein level in Alzheimer’s disease in Taiwanese. Age Ageing 40(2):238–242. doi:10.1093/ageing/afq179 PubMedCrossRef

Zhang JW, Li XQ, Zhang ZX, Chen D, Zhao HL, Wu YN, Qu QM (2005) Association between angiotensin-converting enzyme gene polymorphism and Alzheimer’s disease in a Chinese population. Dement Geriatr Cogn Disord 20(1):52–56. doi:10.1159/000085075 PubMedCrossRef

Title: Angiotensin-converting enzyme gene insertion-deletion polymorphism is a risk marker for Alzheimer’s disease in a Chinese population: a meta-analysis of case–control studies
Authors: Ye Yuan
Jin-hua Piao
Ke Ma
Na Lu
Publication date: 01-08-2015
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 8/2015
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-015-1368-6

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Angiotensin-converting enzyme gene insertion-deletion polymorphism is a risk marker for Alzheimer’s disease in a Chinese population: a meta-analysis of case–control studies

Abstract

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Abstract

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