Homogeneous assay of rs4343, an ACE I/D proxy, and an analysis in the British Women's Heart and Health Study (BWHHS)

Dis Markers. 2008;24(1):11-7. doi: 10.1155/2008/813679.


Current literature suggests that ACE SNP rs4343, ACE 2350A>G in exon 17, T202T, may be the best proxy for the ACE Alu I/D whereas rs4363 and rs4362 may be slightly stronger predictors of ACE levels. Considering reported difficulties in genotyping ACE I/D and stronger associations of rs4343 than ACE I/D with plasma ACE levels 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) with ACE I/D in Europeans (A and G alleles of rs4343 marking insertion and deletion alleles of ACE I/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 that ACE I/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 based ACE I/D genotyping both for technical and functional reasons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Blood Pressure
  • Cardiovascular Diseases / enzymology*
  • Cardiovascular Diseases / genetics
  • DNA / analysis
  • Female
  • Genotype
  • Humans
  • INDEL Mutation*
  • Linkage Disequilibrium / genetics
  • Metabolic Syndrome / enzymology
  • Middle Aged
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / genetics*
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • RNA, Messenger / analysis
  • United Kingdom
  • Women's Health*


  • RNA, Messenger
  • DNA
  • Peptidyl-Dipeptidase A