Trans-ethnic fine mapping of a quantitative trait locus for circulating angiotensin I-converting enzyme (ACE)

Circulating angiotensin I-converting enzyme (ACE) levels are influenced by a major quantitative trait locus (QTL) that maps to the ACE gene. Phylogene tic 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' por tion of the gene has prevented further resolution of the QTL in Caucasian s ubjects. We have examined 10 ACE gene polymorphisms in Afro-Caribbean famil ies recruited in Jamaica. Variance components analyses showed strong eviden ce of linkage and association to circulating ACE levels. When the linkage r esults were contrasted with those from a set of British Caucasian families, there was no evidence for heterogeneity between the samples. However, patt erns 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 diseq uilibrium with the ACE-linked QTL, In the Jamaican families, only marker G2 350A showed strong but incomplete disequilibrium with the ACE-linked QTL, T hese results suggest that additional unobserved polymorphisms have an effec t on circulating ACE levels in Jamaican families. Furthermore, our results show that a variance components approach combined with structured, quantita tive comparisons between families from different ethnic groups may be a use ful strategy for helping to determine which, if any, variants in a small ge nomic region directly influence a quantitative trait.