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
Richard G. IJzerman,
Coen D. A. Stehouwer,
Mirjam M. van Weissenbruch,
Eco J. de Geus and
Dorret I. Boomsma
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 lowweight
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 twinpairs. Regression analysis
demonstrated that low birth weightwas associated with high levels of
total cholesterol, low-densitylipoprotein (LDL) cholesterol and
apolipoprotein B (-0.17 mmol/literper kg, P =
0.07; -0.18 mmol/liter per kg, P = 0.04; and
-0.07g/liter per kg, P = 0.02, respectively) and
with low levelsof high-density lipoprotein (HDL) cholesterol (+0.04
mmol/literper kg, P = 0.1), after adjustment for
age, sex, and body massindex. Intrapair differences in birth weight
were significantlyassociated with differences in total cholesterol,
LDL cholesterol,and apolipoprotein B in dizygotic twins after
adjustment fordifferences in current body mass index (-0.49
mmol/liter perkg, P = 0.02; -0.51 mmol/liter per
kg, P = 0.01; and -0.10 g/literper kg,
P = 0.04, respectively), demonstrating that the
largerthe difference in birth weight, the higher these risk factorsin
the twin with the lower birth weight, compared with the cotwinwith the
higher birth weight. In monozygotic twins, however,the associations
between intrapair differences in birth weightand differences in total
cholesterol, LDL cholesterol, and apolipoproteinB 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/literper
kg, P = 0.04, respectively). The association
between intrapairdifferences in birth weight and differences in HDL
cholesterolwas not significant in dizygotic twins (+0.04 mmol/liter
perkg, P = 0.6) and of borderline significance in
monozygotic twins(+0.11 mmol/liter per kg, P =
0.05). These data suggest thatgenetic factors account for the
association of low birth weightwith high levels of total cholesterol,
LDL cholesterol, andapolipoprotein B, whereas intrauterine factors
possibly playa role in the association between birth weight and HDL
cholesterol.
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