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Contenido archivado el 2024-04-16

IMPORTANCE AND INTERACTION OF GENETIC AND ENVIRONMENTAL FACTORS IN THE DEVELOPMENT OF ATHEROSCLEROSIS

Objetivo

The major objective of the study was to investigate the expression of a parental history of premature coronary heart disease (CHD) in student populations that are exposed to different environments in Europe.
A project was designed to quantify the contributions which heredity and environment make to coronary risk in different populations in Europe and to determine which carries greater weight in increasing the risk of those individuals who are particulary susceptible to coronary heart disease (CHD) in each population.
682 students aged between 18 and 26 years, whose fathers have proven CHD before the age of 55 years (cases), and 1312 age and sex matched controls were recruited and studied from 14 universities in Europe. The recruitment centres were grouped on the basis of CHD mortality rates, geographical location and language into 5 regions: Finland, Great Britain, Northern, Middle and Southern Europe.

A very biologically significant and unexpected finding of the study is that the male offspring of men with premature CHD differ from controls in that they are not as tall, have a higher body mass index, a higher waist hip ratio and increased plasma concentrations of triglyceride as well as cholesterol, low density lipoprotein (LDL) cholesterol and apolipoprotein B. These differences were not manifested in the female offspring of men with premature CHD. These findings suggest that insulin resistance, as manifested in the so called 'syndrome X' could be the major familial trait responsible for CHD. This clearly is of immense importance and needs to be confirmed and more rigorously investigated.

It is clear from the genetic studies in the study that while there are genetic differences detectable in the different populations throughout Europe, at present, no satisfactory genetic marker is emerging for CHD. Though familial hypercholesterolaemia is a well established cause of premature CHD its contribution globally to the problem of CHD appears not to be very marked, as it did not emerge as a significant difference between cases and controls in this study.

The study was also successful in its goal in assessing the interaction of genetic and environmental factors, in that it was clear the lifestyle and dietary habits of the offspring of men with premature CHD is determined by their cultural background and environment, and their behaviour is no different from that of their peers without a family history of CHD.

The study elegantly showed gene gene interaction in that the influence of apoE phenotype on apoB plasma concentration was consistently manifested throughout Europe.
Coronary heart disease (CHD), the most common cause of death and disability in Europe, is unevenly distributed among countries within Europe. Environmental factors have been identified that explain part of this between population different in prevalence and incidence. Among these, nutritional factors, smoking habits and physical activity pattern seem to be of crucial importance. Risk prediction on an individual basis is more difficult since genetic predisposition or protection are clearly involved.

The project was designed to attempt to quantify the contributions which heredity and environment make to coronary risk in different populations in Europe and to determine which carries greater weight in increasing the risk of those individuals who are particularly susceptible to CHD in each population.

More specifically:
Within Student Populations
Differences between cases, students with a parental history of premature CHD, and age and sex-matched controls in:
(a) Genetic markers (eg certain RFLPs).
(b) Lifestyles (eg smoking habits, exercise, diet etc).
(c) Factors that are both determined by genetics and the environment (eg lipoprotein levels).

Between Student Population
The relative importance of each of the study variables in discriminating cases from controls. It could be hypothesised that in populations where the environment is less prone to CHD (less saturated fat intake for instance) the genetic markers should be more expressed and vice versa. In that sense interactions between genetic and environmental factors were studied.

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Coordinador

Royal Infirmary
Aportación de la UE
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Dirección

G4 0SF Glasgow
Reino Unido

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