Homogeneous assay of rs4343, an ACE I/D proxy, and an analysis in the British Women's Heart and Health Study (BWHHS).
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.
Abdollahi
Mohammad Reza
MR
Bristol Genetic Epidemiology Laboratory, University of Bristol, No. 24 Tyndall Avenue, Bristol, BS8 1TQ, UK. medmra@leeds.ac.uk
Huang
Shuwen
S
Rodriguez
Santiago
S
Guthrie
Philip Alexander Isles
PA
Smith
George Davey
GD
Ebrahim
Shah
S
Lawlor
Debbie A
DA
Day
Ian N M
IN
Gaunt
Tom R
TR
D000368:Aged; D000483:Alleles; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000235:genetics; D004247:DNA / Q000032:analysis; D005260:Female; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D015810:Linkage Disequilibrium / Q000235:genetics; D024821:Metabolic Syndrome / Q000201:enzymology; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D006113:United Kingdom; D016387:Women's Health
D012333:RNA, Messenger; D004247:DNA; D007703:Peptidyl-Dipeptidase A