Background--Lipoprotein and weight differences between vigorously active and sedentary monozygotic (MZ) twins were used to (1) estimate the effects of training while controlling for genotype and (2) estimate genetic concordance (ie, similarity) in the presence of divergent lifestyles.

Methods and Results--Thirty-five pairs of MZ twins (25 male, 10 female) were recruited nationally who were discordant for vigorous exercise (running distances differed by 40 km in male and 32 km in female twins). The active twins ran an average (mean±SD) of 63.0±20.4 km/wk, whereas the mostly sedentary twins averaged 7.0±13.5 km/wk. The active twins had significantly lower body mass index (difference±SE, -2.12±0.57 kg/m², P=0.0007) and significantly higher HDL cholesterol (0.14±0.04 mmol/L, P=0.004), HDL₂ (2.71±1.04 U, P=0.01), and apolipoprotein (apo) A-I (0.10±0.03 g/L, P=0.004). Despite the difference in lifestyle, when adjusted for sex, the correlations between the discordant MZ twin pairs were significant (P<0.01) for HDL cholesterol (r=0.69), apoA-I (r=0.58), and HDL₂ (r=0.67). There was no significant MZ twin correlation for body mass index (r=0.17). None of the active twins having an overweight twin were themselves overweight.

Conclusions--Behavior (vigorous exercise) may reduce genetic influences on body mass index. In contrast, genetics (or shared environment) substantially influences HDL cholesterol and HDL subclasses, even in the presence of extreme behavioral differences. There may be greater individual control over moderate degrees of obesity, whereas low HDL cholesterol may be largely predetermined and less effectively treated by vigorous exercise.