Homogeneous Assay of rs4343, anACEI/D Proxy, and an Analysis in the British Women’s Heart and Health Study (BWHHS)

Abstract

Current literature suggests thatACESNP rs4343,ACE2350A>G in exon 17, T202T, may be the best proxy for theACEAlu I/D whereas rs4363 and rs4362 may be slightly stronger predictors ofACElevels. Considering reported difficulties in genotypingACEI/D and stronger associations of rs4343 thanACEI/D with plasmaACElevels in Africans, and suitability of rs4343 for allelic mRNA (cDNA) studies, we developed and validated a liquid phase assay for rs4343, which has advantage on both functional and technical grounds. We confirmed that rs4343, is in near perfect linkage disequilibrium (D’=1, r2=0.88, n=64) withACEI/D in Europeans (A and G alleles of rs4343 marking insertion and deletion alleles ofACEI/D respectively).We then studied its association with metabolic and cardiovascular traits in 3253 British women (60–79 years old).Apart from a nominal trend of association with diastolic blood pressure (p anova=0.08; p trend=0.05), no other associations were observed. A post-hoc vascular and general phenome scan revealed no further associations.We conclude thatACEI/D is not a major determinant of metabolic and cardiovascular traits in this population. Liquid phase genotyping of SNP rs4343 may be preferable to gel basedACEI/D genotyping both for technical and functional reasons.