B647 - Blood vessels and patterns of brain function in twins - 17/04/2008

B number: 
Principal applicant name: 
Atul Singhal (Institute of Child Health, University College London, UK)
Prof John Deanfield (Not used -1, Not used -1)
Title of project: 
Blood vessels and patterns of brain function in twins
Proposal summary: 

Vascular function and cardiovascular risk factors in twins

The twin study was conducted in collaboration with the Multiple birth foundation and, for measures of vascular function, with Professor John Deanfield. We have recruited 210 pairs but require a further 20 pairs (particularly DZ twins). As we have exhausted the available twins from the multiple birth foundation we require additional data from twins collected as part of Professor John Deanfield's collaboration with ALSPAC. These cross-sectional data are already available in Professor's Deanfield's database of the ALSPAC cohort (eg measures of vascular function, demographic and anthropometric data, and conventional cardiovascular risk factors). We require only the identification of twins from this existing database and the method by which the zygosity was determined. We do not require any personal data. This will allow us to include the small number of twins (previously estimated as less than 25 pairs) collected as part of Professor Deanfield's collaboration with ALSPAC to be included in our study and hence achieve our sample size. All vascular measures in both studies have been made using identical techniques.

The twin study was funded by the MRC to test the following 2 hypothesis:

1. In twins discordant for birth weight we tested the hypothesis that low birth-weight is associated with endothelial dysfunction independent of maternal factors and the family environment (including socio-economic status). A twin study in children as opposed to adults allowed us to investigate early stages of atherosclerosis before the onset of lifestyle cardiovascular risk factors common in adulthood. This study has now been completed.

2. That the childhood environment strongly affects development of early atherosclerosis and its risk factors. Justification: Our own and other's data, suggest the atherosclerotic process may begin even in the first decade. But, the relative contributions of genetic and environmental factors to early atherosclerosis (as opposed to clinical CVD) are unknown. A classical twin model in children allow us to define the relative impact of additive genetic factors, and both shared and non-shared environmental factors on early atherosclerosis. The Framingham study (with a less robust family-based rather than twin study design) suggests that inherited genetic factors make a small contribution to early atherosclerosis. Similarly, our preliminary twin data suggest that shared environmental factors (including family environment and nutritional habits) have a major impact on arterial distensibility, while additive genetic factors make little contribution. Outcomes: In same-sex twin pairs aged 6-18years we have determined measures of vascular health such as flow mediated dilation, arterial distensibility and conventional CVD risk factors such as cholesterol concentration, insulin resistance, C-reactive protein concentration and leptin resistance. The relative contribution of additive genetic versus environmental factors to these outcomes will be assessed using published approaches. We require a further DZ twin pairs to complete this study.

Date proposal received: 
Thursday, 17 April, 2008
Date proposal approved: 
Thursday, 17 April, 2008
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