Key result
The ACE SNP rs4343 genotype was not significantly associated with metabolic or cardiovascular traits in older British women, aside from a nominal trend of 1 mmHg higher diastolic blood pressure with the GG genotype.
Why the study?
Is the ACE SNP rs4343 associated with metabolic and cardiovascular traits in older British women?
Observational (n=3,253)
Is the ACE SNP rs4343 associated with metabolic and cardiovascular traits in older British women?
The ACE I/D polymorphism proxy rs4343 is not a major determinant of metabolic and cardiovascular traits in older British women, though liquid phase genotyping of this SNP offers technical advantages.
rs4343 should not guide risk assessment in older women; leaves open ACE variant effects in other populations or settings.
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.
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Abdollahi et al. (2007) conducted an observational in Cardiovascular and metabolic traits (n=3,253). ACE SNP rs4343 (ACE 2350A>G) genotype vs. Between genotype groups (AA vs GA vs GG) was evaluated on Diastolic blood pressure (mmHg) (p=0.08). The ACE SNP rs4343 genotype was not significantly associated with metabolic or cardiovascular traits in older British women, aside from a nominal trend of 1 mmHg higher diastolic blood pressure with the GG genotype.
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