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

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, 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.

SUBMITTER: Abdollahi MR

PROVIDER: S-EPMC3850618 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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

Abdollahi Mohammad Reza MR 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

Disease markers 20080101 1

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 an ...[more]

PMID: 18057531

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Project description:Background:Three recent meta-analyses found significant prospective inverse associations between chocolate intake and cardiovascular disease risk. Evidence from these meta-analyses suggests that such inverse associations may only apply to elderly individuals or those with pre-existing major chronic disease. Objective:We assessed the association between habitual chocolate intake and subsequent incident coronary heart disease (CHD) and stroke, and the potential effect of modification by age. Design:We conducted multivariable Cox regression analyses using data from 83,310 postmenopausal women free of baseline pre-existing major chronic disease in the prospective Women's Health Initiative cohort. Chocolate intake was assessed using a food-frequency questionnaire. Physician-adjudicated events or deaths were ascertained up to 30 September 2013. Results:After exclusions, there were 3246 CHD and 2624 stroke events or deaths, representing incidence rates of 3.9% and 3.2% during 1,098,091 and 1,101,022 person-years (13.4 y), respectively. We found no association between consumption of chocolate and risk of CHD (P for linear trend = 0.94) or stroke (P = 0.24). The results for CHD and stroke combined were similar (P = 0.30), but were significantly modified by age (P for interaction = 0.02). For women age <65 y at baseline, those who ate 1 oz (28.35 g) of chocolate <1/mo, 1 to <1.5/mo, 1.5 to <3.5/mo, 3.5/mo to <3/wk, and ?3/wk had HRs (95% CIs) of 1.00 (referent), 1.17 (1.00, 1.36), 1.05 (0.90, 1.22), 1.09 (0.94, 1.25), and 1.27 (1.09, 1.49), respectively (P for linear trend = 0.005). No association was apparent for older women. Conclusion:We observed no association between chocolate intake and risk of CHD, stroke, or both combined in participants free of pre-existing major chronic disease. The relation for both combined was modified by age, with a significant positive linear trend and an increased risk in the highest quintile of chocolate consumption among women age <65 y. This trial was registered at clinicaltrials.gov as NCT03453073.

Dataset Information

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

Publications

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

Similar Datasets

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