Introduction Directory UMM :Data Elmu:jurnal:A:Atherosclerosis:Vol152.Issue2.Oct2000:

Atherosclerosis 152 2000 135 – 141 Apolipoprotein E4 phenotype increases non-fasting serum triglyceride concentration in infants — the STRIP study Anne Tammi a, , Tapani Ro¨nnemaa b , Jorma Viikari b , Eero Jokinen c , Helena Lapinleimu d , Christian Ehnholm e , Olli Simell d a Cardiorespiratory Research Unit, Uni6ersity of Turku, Kiinamyllynkatu 10 , FIN- 20520 Turku, Finland b Department of Medicine, Uni6ersity of Turku, Kiinamyllynkatu 4 – 8 , FIN- 20520 Turku, Finland c Hospital for Children and Adolescents, Uni6ersity of Helsinki, Stenba¨ckinkatu II, FIN- 00290 Helsinki, Finland d Department of Pediatrics, Uni6ersity of Turku, Kiinamyllynkatu 4 – 8 , FIN- 20520 Turku, Finland e National Public Health Institute, P.B. 450 , FIN- 00101 Helsinki, Finland Received 25 January 1999; received in revised form 28 September 1999; accepted 15 October 1999 Abstract As genetically determined apolipoprotein E apo E phenotypes influence serum cholesterol concentration, we analysed whether serum triglyceride values are also affected by the apo E phenotypes in infants. Non-fasting serum triglyceride values were measured in 7- and 13-month-old participants in the STRIP project, a randomised, prospective trial aimed at reducing children’s exposure to known atherosclerosis risk factors n = 1062. The mean 9 S.D. non-fasting serum triglyceride concentrations in 7-month-old infants with apo E44 n = 36, E34 n = 209, E33 n = 412, and E23 n = 66 were 2.05 9 1.24, 1.81 9 0.90, 1.63 9 0.90, and 1.71 9 0.83 mmoll, respectively. Triglyceride concentrations were higher in infants with apo E44 or 34 than in those with apo E33 P-value for difference 0.01 and 0.009, respectively. The apo E phenotype similarly influenced non-fasting serum triglyceride concentrations at the age of 13 months. The differences in serum triglyceride values in apo E4 + infants apo E34 and 44 infants combined and apo E4 − infants apo E23 and 33 infants combined occurred independently of the relative weight of the infant, milk type used at 7 months of age breast milk or formula, and time elapsed from the previous meal. To conclude, apo E phenotypes regulate non-fasting serum triglyceride values in healthy infants. Apo E34 and apo E44 predispose infants to higher values than apo E33 phenotype, suggesting that the o4 allele may increase atherosclerosis risk also via it’s effect on postprandial triglyceride metabolism. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords : Triglycerides; Apo E; Infants; Breast milk; Cholesterol www.elsevier.comlocateatherosclerosis

1. Introduction

Apolipoprotein E apo E is a constituent of triglyce- ride rich lipoproteins i.e. chylomicrons, very low den- sity lipoproteins and their remnants and some subclasses of high density lipoproteins HDL [1]. The gene for human apo E is polymorphic; the three com- mon alleles o2, o3, and o4 encode the isoproteins E2, E3, and E4, respectively. The homozygous phenotypes E22, E33, and E44 and the heterozygous phenotypes E23, E24, and E34 thus predominate [2]. Apo E acts as a ligand for low density lipoprotein LDL and remnant receptors, thus playing an impor- tant role in the metabolism of cholesterol and triglyce- ride rich lipoproteins [1]. Apo E also participates in catabolism of chylomicrons together with lipoprotein lipase LPL, independently of the LDL receptor [3] and is involved in the conversion of intermediate den- sity lipoprotein to LDL [4]. The association between the apo E phenotypes and serum total and LDL cholesterol concentrations is well established. On average, subjects with apo E2 have lower and those with apo E4 higher serum total and LDL cholesterol concentration than those with apo E3 [5 – 8]. The association between the apo E phenotypes and serum triglyceride values has remained less clear. Corresponding author. Tel.: + 358-2-333-7306; fax: + 358-2-233- 1126. E-mail address : anne.tammiutu.fi A. Tammi. 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 1 - 9 1 5 0 9 9 0 0 4 3 6 - 0 The prevalence of o2 allele is increased in individuals with hypertriglyceridemia [9,10] and clearance of triglyceride rich particles is prolonged also in nor- molipidemic individuals with one or two o2 alleles [11,12]. E22 phenotype is an obligatory, but not the only, prerequisite for the development of human type III hyperlipidemia, characterised by accumulation of remnants of triglyceride rich lipoprotein particles in plasma [13]. However, this rare condition alone fails to explain the o2-hypertriglyceridemia association. A few studies suggest that o4 carriers also have higher serum triglyceride values than o3 homozygotes [14 – 18], and the meta-analysis by Dallongeville and co- workers shows that subjects with apo E2 phenotype and apo E4 heterozygotes have higher serum triglyce- ride concentrations than E3 homozygotes [19]. To analyse the effects of the apo E phenotypes on serum triglyceride values in breast-fed and recently weaned infants, serum triglyceride values and apo E phenotypes were determined in a large population of 7- and 13-month-old infants in Finland, a country with an exceptionally high prevalence of the o4 allele.

2. Methods