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Evidence for Genetic Factors Explaining the Association Between Birth Weight and Low-Density Lipoprotein Cholesterol and Possible Intrauterine Factors Influencing the Association Between Birth Weight and High-Density Lipoprotein Cholesterol: Analysis in Twins

Department of Internal Medicine and Institute for Cardiovascular Research-Vrije Universiteit (R.G.IJ., C.D.A.S.) and Department of Paediatrics and Institute for Endocrinology, Reproduction, and Metabolism (R.G.IJ., M.M.W.), Academic Hospital Vrije Universiteit; and the Department of Biological Psychology, Vrije Universiteit (E.J.G., D.I.B.), Amsterdam 1007 MB, The Netherlands

Address all correspondence and requests for reprints to: Professor Coen D. A. Stehouwer, Department of Medicine, Academic Hospital Vrije Universiteit, De Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: cda.stehouwer{at}azvu.nl

Abstract

Recent studies have demonstrated an association between low weight at birth and an atherogenic lipid profile in later life. To examine the influences of intrauterine and genetic factors, we investigated 53 dizygotic and 61 monozygotic adolescent twin pairs. Regression analysis demonstrated that low birth weight was associated with high levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and apolipoprotein B (-0.17 mmol/liter per kg, P = 0.07; -0.18 mmol/liter per kg, P = 0.04; and -0.07 g/liter per kg, P = 0.02, respectively) and with low levels of high-density lipoprotein (HDL) cholesterol (+0.04 mmol/liter per kg, P = 0.1), after adjustment for age, sex, and body mass index. Intrapair differences in birth weight were significantly associated with differences in total cholesterol, LDL cholesterol, and apolipoprotein B in dizygotic twins after adjustment for differences in current body mass index (-0.49 mmol/liter per kg, P = 0.02; -0.51 mmol/liter per kg, P = 0.01; and -0.10 g/liter per kg, P = 0.04, respectively), demonstrating that the larger the difference in birth weight, the higher these risk factors in the twin with the lower birth weight, compared with the cotwin with the higher birth weight. In monozygotic twins, however, the associations between intrapair differences in birth weight and differences in total cholesterol, LDL cholesterol, and apolipoprotein B were in the opposite direction (+0.32 mmol/liter per kg, P = 0.03; +0.23 mmol/liter per kg, P = 0.08; and +0.06 g/liter per kg, P = 0.04, respectively). The association between intrapair differences in birth weight and differences in HDL cholesterol was not significant in dizygotic twins (+0.04 mmol/liter per kg, P = 0.6) and of borderline significance in monozygotic twins (+0.11 mmol/liter per kg, P = 0.05). These data suggest that genetic factors account for the association of low birth weight with high levels of total cholesterol, LDL cholesterol, and apolipoprotein B, whereas intrauterine factors possibly play a role in the association between birth weight and HDL cholesterol.

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