ALFRED: allele frequency database

The ALlele FREquency Database
ALFRED is a resource of gene frequency data on human populations
supported by the U. S. National Science Foundation.

ALFRED detailed record information

Locus Information

Name	ALFRED UID	Locus Symbol	Chromosome	Band Position
Angiotensin I converting enzyme (peptidyl-dipeptidase A) 1	LO000205H	ACE	17	17q23

Synonyms: DCP1 ; dipeptidyl carboxypeptidase 1 (angiotensin I converting enzyme) ; DCP ; ACE1 ;
Sites List: See Sites List
External Resources: Entrez Gene Locus Information OMIM description GenBank sequence UniGene PharmGKB Gene Information Genopedia (HuGE Navigator)
References: See References
Locus Description: The nomenclature committee has changed the locus symbol back to ACE from the now obsolete DCP1. Angiotensin-converting enzyme (ACE, also known as dipeptidyl carboxypeptidase 1) is encoded by a single gene (DCP1) on chromosome 17q23 (Mattei et al., 1989). It is a metalloprotease that is distributed throughout the body, both membrane bound and in circulation. ACE plays an important role in the regulation of blood pressure via the renin-angiotensin-aldosterone system (RAAS). It converts angiotensin I, a stable, mild vasoconstrictor, into angiotensin II, a transient, potent vasoconstrictor and a stimulant of aldosterone release. ACE also inactivates the vasodilator bradykinin. A number of polymorphic loci have been identified in the ACE gene (Zhu et al., 2001) [PubMed ID: 11283791]. The most studied of these is the Alu "insertion/deletion" in intron 16. The presence of the 287 bp alu fragment (the insertion, or I, allele) is associated with decreased ACE levels (Rigat et al., 1990) [PubMed ID: 1976655]. Alleles at this locus have been associated with such diverse "phenotypes" as cardiovascular disease (reviewed by Danser and Schunkert, 2000 [PubMed ID: 11134678]), erectile dysfunction (Park et al., 1999) [PubMed ID: 10553806], athletic performance (Gayagay et al., 1998) [PubMed ID: 9737775], Alzheimer's disease susceptibility (Kehoe et al., 1999) [PubMed ID: 9916793], and mountaineering success (Montgomery et al., 1998) [PubMed ID: 9607758]. Not all studies however have detected a phenotype associated with the ACE I/D alleles (see for example Rankinen et al., 2000 [PubMed ID: 10797114], Jeunemaitre et al., 1997 [PubMed ID: 9003497], and Winkelmann et al., 2000 [PubMed ID: 11011311]) and the reader should be aware that there is much discussion in the scientific literature about the physiological impact, if any, of alleles at this locus. It is of interest that several groups have reported synergistic interactions between alleles at the I/D polymorphism and alleles at polymorphic loci in genes encoding other components of the RAAS system (for example: Tiret et al., 1994 [PubMed ID: 7934345] and Hingorani et al., 1995 [PubMed ID: 8903618]).
Sites within this locus ordered by their chromosomal position in the 37.3 NCBI build:

Site Name (Navigates to ALFRED description)	dbSNP rs# (Navigates to dbSNP reference page)	Chr-Position	# Populations typed
rs4362	rs4362	0	40
rs4343	rs4343	58919763	5
5-site haplotype		61550529	1
rs1800764	rs1800764	61550529	1
rs7214530	rs7214530	61551605	50
rs4291	rs4291	61554194	2
rs4305	rs4305	61558229	51
rs4309	rs4309	61559923	52
rs4311	rs4311	61560763	51
rs4329	rs4329	61563458	51
rs4331	rs4331	61564052	1
Ya5NBC102 Alu insertion		61565901	15
ACE Alu indel	rs4646994	61565904	196
rs4343	rs4343	61566031	52
C____589818_10	rs4353	61570422	72
rs4362	rs4362	61573761	50
rs4461142	rs4461142	61578048	51

References:
- Danser AH, Schunkert H. "Renin-angiotensin system gene polymorphisms: potential mechanisms for their association with cardiovascular diseases". Eur. J. Pharmacol. 410:303-316. (2000) Online citation.

- Gayagay G, Yu B, Hambly B, Boston T, Hahn A, Celermajer DS, Trent RJ. "Elite endurance athletes and the ACE I allele--the role of genes in athletic performance". Hum. Genet. 103:48-50. (1998) Online citation.

- Goddard KA, Hopkins PJ, Hall JM, Witte JS. "Linkage Disequilibrium and Allele-Frequency Distributions for 114 Single-Nucleotide Polymorphisms in Five Populations ". Am. J. Hum. Genet. 66:216-234. (2000) Online citation.

- Hingorani AD, Jia H, Stevens PA, Hopper R, Dickerson JE, Brown MJ. "Renin-angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition". J. Hypertens. 13:1602-9. (1995) Online citation.

- Jeunemaitre X, Ledru F, Battaglia S, Guillanneuf MT, Courbon D, Dumont C, Darmon O, Guize L, Guermonprez JL, Diebold B, Ducimetiere P. "Genetic polymorphisms of the renin-angiotensin system and angiographic extent and severity of coronary artery disease: the CORGENE study". Hum. Genet. 99:66-73. (1997) Online citation.

- 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. "Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease". Nat. Genet. 21:71-2. (1999) Online citation.

- Montgomery HE, Marshall R, Hemingway H, Myerson S, Clarkson P, Dollery C, Hayward M, Holliman DE, Jubb M, World M, Thomas EL, Brynes AE, Saeed N, Barnard M, Bell JD, Prasad K, Rayson M, Talmud PJ, Humphries SE. "Human gene for physical performance". Nature 393:221-2. (1998) Online citation.

- Park JK, Kim W, Kim SW, Koh GY, Park SK. "Gene-polymorphisms of angiotensin converting enzyme and endothelial nitric oxide synthase in patients with erectile dysfunction". Int. J. Impot. Res. 11:273-6. (1999) Online citation.

- Rankinen T, Wolfarth B, Simoneau JA, Maier-Lenz D, Rauramaa R, Rivera MA, Boulay MR, Chagnon YC, Perusse L, Keul J, Bouchard C. "No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status". J. Appl. Physiol. 88:1571-5. (2000) Online citation.

- Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. "An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels". J. Clin. Invest. 86:1343-6. (1990) Online citation.

- Rupert JL, Devine DV, Monsalve MV, Hochachka PW. "Angiotensin-converting enzyme (ACE) alleles in the Quechua, a high altitude South American native population". Ann. Hum. Biol. 26:375-80. (1999) Online citation.

- Tiret L, Bonnardeaux A, Poirier O, Ricard S, Marques-Vidal P, Evans A, Arveiler D, Luc G, Kee F, Ducimetiere P, et al. "Synergistic effects of angiotensin-converting enzyme and angiotensin-II type 1 receptor gene polymorphisms on risk of myocardial infarction". Lancet 344:910-3. (1994) Online citation.

- Winkelmann BR, Hager J, Kraus WE, Merlini P, Keavney B, Grant PJ, Muhlestein JB, Granger CB. "Genetics of coronary heart disease: current knowledge and research principles". Am. Heart. J. 140:S11-26. (2000) Online citation.

- Zhu X, Bouzekri N, Southam L, Cooper RS, Adeyemo A, McKenzie CA, Luke A, Chen G, Elston RC, Ward R. "Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure". Am. J. Hum. Genet. 68:1139-48. (2001) Online citation.

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© 2012 Kenneth K Kidd, Yale University. All rights reserved. The full Copyright Notification is also available.
Originally prototyped by Michael Osier with the aid of Kei Cheung
Upgrades and maintenance since 2002 by Haseena Rajeevan