The impact of genes and pre- and postnatal environment on the metabolic syndrome. Evidence from twin studies

Abstract

Our population-based Danish twin study demonstrated a genetic influence on several of the components included in the metabolic syndrome, i.e. glucose intolerance, overall obesity, systolic and diastolic blood pressure and low levels of HDL-cholesterol. Abdominal obesity, insulin resistance and hypertriglyceridaemia had, on the other hand, a relatively higher environmental aetiological component. Furthermore we demonstrated a difference in aetiology among male and female twins indicating an influence of sex on several of the components in the metabolic syndrome. Studies have demonstrated an impact of the intrauterine environment (i.e. low birth weight) for the development of the components in the metabolic syndrome. The validity of conclusions drawn from classical twin studies has therefore been questioned due to the different prenatal circumstances characterising monozygotic (MZ) and dizygotic (DZ) pregnancies. Due to a potentially more adverse intrauterine environment among MZ compared to DZ twins, MZ twins may be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profiles after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake--indicating glucose intolerance and insulin resistance--together with higher levels of total-cholesterol and triglycerides among MZ compared to DZ twins demonstrate an effect of zygosity (i.e. intrauterine environment) on these metabolic variables and therefore question the assumption of equal pre- and postnatal environment in MZ and DZ twins. Our studies provide further evidence for a prenatal component in the aetiology of the components included in the syndrome and question the validity of classical twin studies on phenotypes with a known prenatal aetiological component. However, our present knowledge is currently far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of the metabolic and haemodynamic components included in the metabolic syndrome.