A genome-wide search replicates evidence of a quantitative trait locus for circulating angiotensisn l-converting enzyme (ACE) unlinked to the ACE gene
A genome-wide search replicates evidence of a quantitative trait locus for circulating angiotensisn l-converting enzyme (ACE) unlinked to the ACE gene
Background: angiotensin I-converting enzyme (ACE) plays an important role in cardiovascular homeostasis. There is evidence from different ethnic groups that circulating ACE levels are influenced by a quantitative trait locus (QTL) at the ACE gene on chromosome 17. The finding of significant residual familial correlations in different ethnic groups, after accounting for this QTL, and the finding of support for linkage to a locus on chromosome 4 in Mexican-American families strongly suggest that there may well be QTLs for ACE unlinked to the ACE gene.
Methods: a genome-wide panel of microsatellite markers, and a panel of biallelic polymorphisms in the ACE gene were typed in Nigerian families. Single locus models with fixed parameters were used to test for linkage to circulating ACE with and without adjustment for the effects of the ACE gene polymorphisms.
Results: strong evidence was found for D17S2193 (Zmax = 3.5); other nearby markers on chromosome 17 also showed modest support. After adjustment for the effects of the ACE gene locus, evidence of "suggestive linkage" to circulating ACE was found for D4S1629 (Zmax = 2.2); this marker is very close to a locus previously shown to be linked to circulating ACE levels in Mexican-American families.
Conclusion: in this report we have provided further support for the notion that there are QTLs for ACE unlinked to the ACE gene; our findings for chromosome 4, which appear to replicate the findings of a previous independent study, should be considered strong grounds for a more detailed examination of this region in the search for genes/variants which influence ACE levels.
The poor yields, thus far, in defining the genetic determinants of hypertension risk suggest a need to look beyond simple relationships between genotypes and the ultimate phenotype. In addition to incorporating information on important environmental exposures, a better understanding of the factors which influence the building blocks of the blood pressure homeostatic network is also required. Detailed studies of the genetic determinants of ACE, an important component of the renin-angiotensin system, have the potential to contribute to this strategic objective
23-[7pp]
McKenzie, Coiln A.
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Zhu, Xiaofeng
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Forrester, Terrence E.
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Luke, Amy
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Adeyemo, Adebowale A.
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Bouzekri, Nourdine
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Cooper, Richard S.
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June 2008
McKenzie, Coiln A.
9159dd26-160b-4056-9cc1-6ebf08fab38f
Zhu, Xiaofeng
2a0830c8-0c12-4efe-b3c6-11a555c5fa42
Forrester, Terrence E.
d5ed0294-0713-4521-baf9-923f1cae5e7f
Luke, Amy
0b19c645-b4ad-41a6-9f10-6c415b3223a3
Adeyemo, Adebowale A.
5e10623f-c008-48e3-9e75-825d6ae83ba7
Bouzekri, Nourdine
53cbd994-6578-45a2-8410-d92862fbace2
Cooper, Richard S.
2d5c12e7-239d-44bb-8a02-2ca07213bfed
McKenzie, Coiln A., Zhu, Xiaofeng, Forrester, Terrence E., Luke, Amy, Adeyemo, Adebowale A., Bouzekri, Nourdine and Cooper, Richard S.
(2008)
A genome-wide search replicates evidence of a quantitative trait locus for circulating angiotensisn l-converting enzyme (ACE) unlinked to the ACE gene.
BMC Medical Genomics, 10 (1), .
(doi:10.1186/1755-8794-1-23).
Abstract
Background: angiotensin I-converting enzyme (ACE) plays an important role in cardiovascular homeostasis. There is evidence from different ethnic groups that circulating ACE levels are influenced by a quantitative trait locus (QTL) at the ACE gene on chromosome 17. The finding of significant residual familial correlations in different ethnic groups, after accounting for this QTL, and the finding of support for linkage to a locus on chromosome 4 in Mexican-American families strongly suggest that there may well be QTLs for ACE unlinked to the ACE gene.
Methods: a genome-wide panel of microsatellite markers, and a panel of biallelic polymorphisms in the ACE gene were typed in Nigerian families. Single locus models with fixed parameters were used to test for linkage to circulating ACE with and without adjustment for the effects of the ACE gene polymorphisms.
Results: strong evidence was found for D17S2193 (Zmax = 3.5); other nearby markers on chromosome 17 also showed modest support. After adjustment for the effects of the ACE gene locus, evidence of "suggestive linkage" to circulating ACE was found for D4S1629 (Zmax = 2.2); this marker is very close to a locus previously shown to be linked to circulating ACE levels in Mexican-American families.
Conclusion: in this report we have provided further support for the notion that there are QTLs for ACE unlinked to the ACE gene; our findings for chromosome 4, which appear to replicate the findings of a previous independent study, should be considered strong grounds for a more detailed examination of this region in the search for genes/variants which influence ACE levels.
The poor yields, thus far, in defining the genetic determinants of hypertension risk suggest a need to look beyond simple relationships between genotypes and the ultimate phenotype. In addition to incorporating information on important environmental exposures, a better understanding of the factors which influence the building blocks of the blood pressure homeostatic network is also required. Detailed studies of the genetic determinants of ACE, an important component of the renin-angiotensin system, have the potential to contribute to this strategic objective
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Published date: June 2008
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Local EPrints ID: 79360
URI: http://eprints.soton.ac.uk/id/eprint/79360
ISSN: 1755-8794
PURE UUID: 82c88d7d-04ff-41e1-86e9-aa56c048f8d6
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Date deposited: 15 Mar 2010
Last modified: 14 Mar 2024 00:29
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Author:
Coiln A. McKenzie
Author:
Xiaofeng Zhu
Author:
Terrence E. Forrester
Author:
Amy Luke
Author:
Adebowale A. Adeyemo
Author:
Nourdine Bouzekri
Author:
Richard S. Cooper
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