Human Molecular Genetics, 2001, Vol. 10, No. 10 1077-1084
© 2001 Oxford University Press
Trans-ethnic fine mapping of a quantitative trait locus for circulating angiotensin I-converting enzyme (ACE)
1Tropical Metabolism Research Unit, University of the West Indies, Kingston 7, Jamaica, 2The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK, 3MRC Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, UK and 4Centre National de Genotypage, 91057 Evry Cedex, France
Circulating angiotensin I-converting enzyme (ACE) levels are influenced by a major quantitative trait locus (QTL) that maps to the ACE gene. Phylogenetic and measured haplotype analyses have suggested that the ACE-linked QTL lies downstream of a putative ancestral breakpoint located near to position 6435. However, strong linkage disequilibrium between markers in the 3' portion of the gene has prevented further resolution of the QTL in Caucasian subjects. We have examined 10 ACE gene polymorphisms in Afro-Caribbean families recruited in Jamaica. Variance components analyses showed strong evidence of linkage and association to circulating ACE levels. When the linkage results were contrasted with those from a set of British Caucasian families, there was no evidence for heterogeneity between the samples. However, patterns of allelic association between the markers and circulating ACE levels differed significantly in the two data sets. In the British families, three markers [G2215A, Alu insertion/deletion and G2350A] were in complete disequilibrium with the ACE-linked QTL. In the Jamaican families, only marker G2350A showed strong but incomplete disequilibrium with the ACE-linked QTL. These results suggest that additional unobserved polymorphisms have an effect on circulating ACE levels in Jamaican families. Furthermore, our results show that a variance components approach combined with structured, quantitative comparisons between families from different ethnic groups may be a useful strategy for helping to determine which, if any, variants in a small genomic region directly influence a quantitative trait.
+ To whom correspondence should be addressed. Tel: +876 977 6251; Fax: +876 977 0632; Email: camcken@uwimona.edu.jm
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