Both apolipoprotein-E (apo-E) 4 allele and angiotensinconverting enzyme (ACE) deletion (D) polymorphism have been associated with a high risk for coronary heart disease. Increased frequency of the 4 allele has also been reported in patients with late-onset of familial and sporadic Alzheimer's disease (AD). The primary aim of this study is to examine the possible relationship between the ACE gene polymorphism and AD. The second aim of this study is to explore the relation of the ACE and apo-E genotypes with AD. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the apo-E and ACE genotypes.
The frequencies of ACE D and ACE insertion (I) allele among AD patients and controls were 55.7 percent versus 44.2 percent and 51.7 versus 48.2 percent, respectively. Apo-E allele frequencies in the AD group for 2, 3 and 4 were, 1.7 percent, 96.5 percent, and 1.7 percent, respectively. The apo-E allele frequencies of healthy groups for 2, 3 and 4 were 1 percent, 56 percent, and 1.7 percent, respectively.
In conclusion ACE D and apo 4 allele were found to be more frequent in patients with Alzheimer's disease than in the control group.
Strittmatter WJ , Saunders AM, Schmechel D, et al.: Apolipoprotein E: High-avidity binding to -amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Nat Acad Sci.1993; 90: 1977-1981.
2.
Corder EH , Saunders AM, Strittmatter WJ, et al.: Gene dose of apolipoprotein E type 4 allele and risk of Alzheimer's disease in lateonset families. Science. 1993; 26: 921-923.
3.
Mayeux R , Stern Y, Ottman R, et al.: The apolipoprotein 4 allele in patients with Alzheimer's disease. Ann Neurol. 1993; 34: 752-754.
4.
Saunders AM , Strittmatter WJ, Schmechel D, et al.: Association of apolipoprotein E allele 4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 1993; 43: 1467-1472.
5.
Pourier J , Davignon J, Bouthillier D, et al.: Apolipoprotein E polymorphism and Alzheimer's disease. Lancet. 1993; 342: 697-699.
6.
Brousseau T , Legrain S, Berr C, et al.: Conformation of the 4 allele of the apolipoprotein E gene as a risk factor for late-onset Alzheimer's disease. Neurology. 1994; 44: 342-344.
7.
Boyles JK , Pitas RE, Wilson E, et al.: Apolipoprotein E associated with astrocitic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J Clin Invest.1985; 76: 1501-1513.
8.
Zannis VI , et al.: Proposed nomenclature of apo-E isoproteins, apo-E genotypes and phenotypes. J Lipid Res. 1982; 23: 911-914.
9.
Davignon J , Gregg RE, Sing CF: Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988; 8: 1-21.
10.
Eto M , Watanabe K, Makino I: Increased frequencies of apolipoprotein 2 and 4 alleles in patients with ischemic heart disease. Clin Genet.1989; 36: 183-188.
11.
Isbir T , Yilmaz H, Bihorac A, Akoglu E: Mild-to-moderate hypertension and apolipoprotein E gene polymorphism. Am J Hypertens. 11997; 10(7): 827-828.
12.
Sparks DL , Hunsaker JC, Scheff SW, et al.: Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease. Neurobiol Aging. 1990; 11: 601-607.
13.
Kosunen O , Talasniemi S, Lehtovirta M, et al.: Relation of coronary atherosclerosis and apolipoprotein E genotypes in Alzheimer patients. Stroke. 1995; 26: 743-748.
14.
Tiret L , et al.: 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.1992; 51: 197-205.
15.
Cambien F , et al.: Deletion polymorphism in the gene coding for angiotensin I converting enzyme is a potent risk factor for myocardial infarction. Nature.1992; 359: 641-644.
16.
Isbir T , Yilmaz H, Agaçhan B, et al.: An association between angiotensin converting enzyme gene polymorphism and coronary artery disease. IVBMB Life.1999; 48: 1-3.
Farrer LA , Sherbatich T, Keryanov SA, et al.: Association between angiotensin converting enzyme genotype and Alzheimer disease. Arch Neurol. 2000; 57: 210-214.
19.
McGeer EG , Singh EA: Angiotensin-converting enzyme in cortical tissue in Alzheimer's and some other neurological diseases. Dementia. 1992; 3: 299-303.
20.
Arregui A , Perry EK, Rossor M, Tomlinson BE: Angiotensinconverting enzyme in Alzheimer's disease:Increased activity in caudate nucleus and cortical areas. J Neurochem. 1982; 38: 1490-1492.
21.
McKhann G , Drachman D, Folstein M, et al.: Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group, Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984; 34: 939-944.
22.
Miller SA , Dykes DD, Polesky HS: Simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res. 1988; 16(3): 1215-1215.
23.
Kontula K , Aalto-Setala K, Kuusi T, et al.: Apolipoprotein E polymorphism determined by restriction enzyme analysis of DNA amplified by polymerase chain reaction: Convenient alternative to phenotyping by isoelectric focusing. Clin. Chem.1990; 36(12): 2087-2092.
24.
Rigat B , Hubert C, Corvol P, Soubrier F: PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene. Nucl. Acid Res.1992; 20: 1433-1433.
25.
Marz W , Scharnagl H, Kirca M, et al.: Apolipoprotein E polymorphism is associated with both senile plaque load and Alzheimer type neurofibrillary tangle formation. Ann NY Acad Sci. 1995: 276-280.
26.
Mattu RK , Needham EWA, Galton DJ, et al.: A DNA variant at the angiotensin-converting enzyme gene locus associates with coronary artery disease in the caerphilly heart study. Circulation. 1995; 91: 270-274.
27.
Schachter F , Faure-Delanef L, Guenot F, et al.: Genetic associations with human longevity at the APOE and ACE loci. Nature Genetics. 1994; 6: 29-32.
28.
Ehlers MRW , Riordan JF: Angiotensin-converting enzyme: New concepts concerning its biological role. Biochem. 1989; 28: 5311-5313.
29.
Eisenlohr LC , Bacik I, Bennink JR, et al.: Expression of a membrane protease enhances presentation of endogenous antigens to MHC class I-restricted T lymphocytes. Cell.1992; 71, 963-972.
30.
Bockxmeer FM , Mamotte CDS, Gibbons FA, et al.: Angiotensinconverting enzyme and apolipoprotein E genotypes and restenosis after coronary angioplasty. Circulation. 1995; 92: 2066-2077.
