Influence of Birth Weight on the Apo E Genetic Determinants of Plasma Lipid Levels in Children

Abstract

To evaluate the influence of birth weight on apolipoprotein (apo) E genetic determinants of plasma lipids levels in prepubertal children we studied 933 healthy children (491 males and 442 females) 6 to 8 years old (mean age of 6.7 y), whose weight was recorded at birth. Plasma lipid and apolipoprotein concentrations and apo E genotypes were determined. We observed a greater effect of the apo E polymorphism on total cholesterol (TC), LDL-cholesterol (LDL-C) and especially apo B levels in children with birth weight in the lower tertile compared with those with birth weights in higher tertiles. Taking the ⑀3 allele homozygosity as reference, in boys with birth weights in the low tertile the overall lowering effect of the ⑀2 allele on TC, LDL-C and apo B was greater (10.5% (p Ͻ 0.01), 20.2% (p Ͻ 0.01) and 18.8% (p Ͻ 0.01), respectively) than in those in the highest tertile (5.6% on TC, 10.3% on LDL-C and 12.6% (p Ͻ 0.01) on apo B). A similar trend in this effect between tertiles of birth weight was also observed in girls. For both sexes, linear regression analysis demonstrates a positive and significant interaction between birth weight and ⑀2, which may explain the fact that the decrease in TC, LDL-C and apo B associated with the ⑀2 allele is more marked the lower the birth weight. Taking into account the prevalence of apo E polymorphism, and that appears to be the main genetic factor affecting plasma lipids, the interaction of apo E genotype and birth weight could be an important determinant of TC, LDL-C and apo B levels, and, as a consequence, of atherosclerosis. (Pediatr Res 52: 873-878, 2002) Abbreviations apo, apolipoprotein TC, total cholesterol TG, triglycerides HDL-C, HDL-cholesterol LDL-C, LDL-cholesterol CHD, coronary heart disease Coronary heart disease (CHD) and its risk factors, including abnormalities in lipid metabolism, are associated with small size at birth and low weight during infancy (1, 2). Genetic composition also determines differences in plasma lipid levels and susceptibility to atherosclerosis. Although the risk of CHD due to both environmental and genetic influences is well known, the extent of interactions between these factors has not been well characterized.Apolipoprotein E (apo E) is one of the key regulators of plasma lipid levels by affecting the hepatic binding, uptake, and catabolism of several classes of lipoproteins (3). Apo E genotypes are one of the most important genetic determinants of atherogenesis. Apo E appears in three isoforms E2, E3, and E4, encoded by the corresponding alleles ⑀2, ⑀3, and ⑀4. Previous studies have documented the impact of these mutations on CHD (4 -6) and the effects of these alleles on the normal variation of lipid levels in adult populations. Heterozygous subjects for the ⑀2 and ⑀4 alleles had, respectively, lower and higher total cholesterol (TC) and LDL-C levels than subjects carrying the ⑀3⑀3 genotype (7-9). This influence of the apo E polymorphisms on the metabolism of the apo B-containing lipoproteins appears to be present in the 1st years of li...

Cholesterol and saturated fat intake determine the effect of polymorphisms at ABCG5/ABCG8 genes on lipid levels in children

“…In our population, we previously described an important influence of apoE genotype on TC, LDL-C, and apoB levels, 18,26 but the results reported here remain without significant changes after correcting by this factor (data not shown). The design of our study cannot address the mechanism by which cholesterol or saturated fat interacts with the polymorphisms.…”

“…More detailed information about the design of the study is available in previous publications. 18,19 The study protocol complied with Helsinki Declaration guidelines and Spanish legal provisions governing clinical research on humans, and was approved by the Clinical Research Ethics Committee of the Fundació n Jiménez Díaz in Madrid, Spain. Parents were required to sign a written consent for participation of their children in the study.…”

Relationship of APOA5, PPARγ and HL gene variants with serial changes in childhood body mass index and coronary artery disease risk factors in young adulthood

“…There were no associations between low birth weight and blood lipids in any PPAR-γ2 genotypes. Effect of APOE genotype on total cholesterol, LDL and ApoB has also been reported by others in children with low birth weight [23,24]. The authors suggested that changes in ApoE gene expression may be programmed by in utero nutritional events.…”

ApoE polymorphisms and diarrheal outcomes in Brazilian shanty town children

“…Therefore, it is possible to speculate that increased blood levels of LDL-cholesterol obtained from fat-enriched diets, when available, such as breast-milk, and possibly the enhanced cholesterol absorption from the small intestine (28) likely seen in APOE4 carriers (29), and especially in underweight children (30), would support a rapid developmental catch-up required for optimal development and survival. On the other hand, APOE2 carriers (when not contributing to type III hyperlipidemia) would exhibit lower total cholesterol and LDL-cholesterol levels compared to E3 and E4 bearers (31) and would be at high risk of growth faltering.…”