The association between low birth weight and high levels of cholesterol is not due to increased cholesterol synthesis or absorption: analysis in twins

Low birth weight may be associated with high levels of cholesterol in later life through genetic factors that affect both birth weight and cholesterol metabolism. Alterations in cholesterol synthesis and absorption may play an important role in this association. We examined birth weight and plasma ratios of a precursor of cholesterol, lathosterol (an estimate of cholesterol synthesis), and plant sterols, campesterol and β-sitosterol (estimates of cholesterol absorption), to cholesterol in 53 dizygotic and 58 monozygotic adolescent twin pairs. After adjustment for current weight, birth weight was not associated with the ratios of lathosterol, campesterol, and β-sitosterol either in the overall sample [+0.07 μmol/mmol/kg (95% confidence interval: -0.11 to 0.25), p = 0.5; +0.02 μmol/mmol/kg (-0.33 to 0.37), p = 0.9; and -0.04 μmol/mmol/kg (-0.23 to 0.15), p = 0.8, respectively] or in the intrapair analysis in dizygotic twins [+0.27 μmol/mmol/kg (-0.28 to 0.82), p = 0.3; -0.03 μmol/mmol/kg (-1.07 to 1.01), p = 1.0; and +0.04 μmol/mmol/kg (-0.56 to 0.64), p = 0.9, respectively] or in the intrapair analysis in monozygotic twins [+0.54 μmol/mmol/kg (-0.09 to 1.18), p = 0.09; -0.60 μmol/mmol/kg (-1.59 to 0.39), p = 0.2; and -0.43 μmol/mmol/kg (-0.99 to 0.14), p = 0.14, respectively]. Plasma levels of lathosterol, campesterol, and β-sitosterol, which are indicators of cholesterol synthesis and absorption, thus do not explain the association of low birth weight with high levels of total and LDL cholesterol. As an alternative hypothesis, we suggest that a decrease in cholesterol clearance may play an important role.