The deletion allele (D allele) polymorphism in the angiotensin converting enzyme (ACE) gene is associated with increased levels of the neuropeptide substance P in the basal ganglia and substantia nigra. A reduction of substance P levels in the brain occurs in Parkinson’s disease (PD) and has been implicated in the pathogenesis of the disease. We investigated the hypothesis that the D allele may be protective towards PD by examining the frequency of the ACE (I/D) polymorphism in 178 PD cases (male:female ratio = 1.4) and 192 controls (male:female ratio = 1.5). ACE (I/D) genotype was determined using polymerase chain reaction and 3% agarose gel electrophoresis. Unadjusted chi-square analysis revealed no significant difference between genotype frequencies (χ2 = 3.30, p > 0.10) or allele frequencies (χ2 = 2.52, p > 0.10) between patient and control groups, although PD patients were less likely to be homozygous (OR = 0.80, 95% CI = 0.49–1.29) or heterozygous (OR = 0.80, 95% CI = 0.59–1.06) for the D allele. A stepwise logistic regression analysis of the ACE deletion and risk factor data confirmed that there was no significant association between the ACE deletion (D allele) polymorphism and PD (OR = 0.62, 95% CI = 0.35–1.10, p = 0.10). This study does not support the hypothesis that the D allele of the ACE gene confers a protective effect with respect to PD.

Keywords:
Parkinson’s disease, Angiotensin converting enzyme, Genetics, Polymerase chain reaction
1.
Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, Lesueur-Ginot L, Cohen D: Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 1994;6:29–32.
2.
Cooper R, McFarlane-Anderson N, Bennett FI, Wilks R, Puras A, Tewksbury D, Ward R, Forrester T: ACE, angiotensinogen and obesity: A potential pathway leading to hypertension. J Hum Hypertens 1997;11:107–111.
3.
Forrester T, McFarlane-Anderson N, Bennett FI, Wilks R, Cooper R, Rotimi C, Morrison L, Ward R: The angiotensin converting enzyme and blood pressure in Jamaicans. Am J Hypertens 1997;10:519–524.
4.
Arinami T, Li L, Mitsushio H, Itokawa M, Hamaguchi H, Toru M: An insertion/deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders. Biol Psychiatry 1996;40:1122–1127.
5.
Barker R: Substance P and Parkinson’s disease: A causal relationship? J Theor Biol 1986;120:353–362.
6.
McCann SJ, LeCouteur DG, Green AC, Brayne C, Johnson AG, Chan D, McManus ME, Pond SM: The epidemiology of Parkinson’s disease in an Australian population. Neuroepidemiology 1998;17:310–317.
7.
LeCouteur DG, Leighton PW, McCann SJ, Pond SM: Association of a polymorphism in the dopamine transporter gene with Parkinson’s disease. Mov Disord 1997;12:760–763.
8.
Douglas AM, Georgalis AM, Benton LR, Canavan KL, Atchison BA: Purification of human leukocyte DNA: Proteinase K is not necessary. Anal Biochem 1992;201:362–365.
9.
Evans AE, Poirier O, Kee F, Lecerf L, McCrum E, Falconer T, Crane J, O’Rourke DF, Cambien F: Polymorphisms of the angiotensin-converting enzyme gene in subjects who die from coronary heart disease. Q J Med 1994;87:211–214.
10.
McCann SJ, Pond SM, James KM, LeCouteur DG: Association between polymorphisms in the cytochrome P-450 2D6 gene and Parkinson’s disease: A case-control study and meta-analysis. J Neurol Sci 1997;153:50–53.
11.
Gai WP, Halliday GM, Blumbergs PC, Geffen LB, Blessing WW: Substance P-containing neurons in the mesopontine tegmentum are severely affected in Parkinson’s disease. Brain 1991;114:2253–2267.
12.
Struck LK, Rodnitzky RL, Doleson JK: Stroke and its modification in Parkinson’s disease. Stroke 1990;21:1395–1399.
13.
Iwasaki S, Narabayashi Y, Hamaguchi K, Iwasaki A, Takakusagi M: Cause of death among patients with Parkinson’s disease: A rare mortality due to cerebral haemorrhage. J Neurol 1990;237:77–79.
14.
Levine RL, Jones JC, Bee N: Stroke and Parkinson’s disease. Stroke 1992;23:839–842.
15.
Marttila RJ, Rinne UK: Arteriosclerosis, heredity and some previous infections in the etiology of Parkinson’s disease: A case-control study. Clin Neurol Neurosurg 1976;79:46–56.
16.
Marttila RJ, Rinne UK: Level of blood pressure in patients with Parkinson’s disease: A case-control study. Eur Neurol 1977;16:73–78.
17.
Ueda S, Weir CJ, Inglis GC, Murray GD, Muir KW, Lees KR: Lack of association between angiotensin converting enzyme gene insertion/deletion polymorphism and stroke. J Hypertens 1995;13:1597–1601.
18.
Catto A, Carter AM, Barrett JH, Stickland M, Bamford J, Davies JA, Grant PJ: Angiotensin-converting enzyme insertion/deletion polymorphism and cerebrovascular disease. Stroke 1996;27:435–440.
19.
Arbustini E, Grasso M, Fasani R, Klersy C, Diegoli M, Porcu E, Banchieri N, Fortina P, Danesino C, Specchia G: Angiotensin converting enzyme gene deletion allele is independently and strongly associated with coronary atherosclerosis and myocardial infarction. Br Heart J 1995;74:584–591.
20.
Johnson AG, Simons LA, Friedlander Y, Simons J, Davis DR, McCallum J: I/D polymorphism of the angiotensin-converting enzyme gene does not predict isolated systolic or systolic-diastolic hypertension in the elderly. J Hum Hypertens 1996;10:167–169.
1999
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.