Affiliations: Bristol Genetic Epidemiology Laboratory, University of
Bristol, No. 24 Tyndall Avenue, Bristol, BS8 1TQ, UK | Human Genetics Division, MP 808, Southampton General
Hospital, Tremona Road, Southampton, SO16 6YD, UK | Department of Social Medicine, Canynge Hall,
Whiteladies Road, Bristol, BS8 2PR, UK | Department of Epidemiology & Population Health,
London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E
7HT, UK | Section of Genetics, Leeds Institute of Molecular
Medicine, University of Leeds, St. James's Hospital, Beckett St., Leeds LS9
7TF, UK
Abstract: 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,
r^{2}=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.
Keywords: Angiotensin converting enzyme, insertion deletion polymorphism, metabolic syndrome trait, Alu element, single nucleotide polymorphism
