LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes

Susan J. Murdoch, Andrew P. Boright, Andrew D. Paterson, Bernard Zinman, Michael Steffes, Patricia Cleary, Karen Edwards, Santica S. Marcovina, Jonathan Q. Purnell, John D. Brunzell

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Apo E plays an important role in chylomicron and VLDL remnant processing, uptake or conversion to LDL. The type of lipoprotein that isolates in the LDL density of E2/2 subjects was investigated and the effect of the apo E isoforms on LDL mass was determined in all genotypes in a large group of Type 1 diabetics. Analysis of the LDL composition of E2/2 homozygotes (n = 6) compared to subjects with the common E3/3 isoform (n = 6) demonstrated an enrichment in apo E, unesterified cholesterol, phospholipid and triglyceride relative to apo B in E2/2 subjects, more typical of a dense IDL remnant than of LDL. Although diabetics were studied, these findings are considered to reflect those of the general population. Comparison of the lipoprotein distribution of homozygous and heterozygous subjects revealed that, as genotype changed from E4/4 (n = 22) to E3/4 (n = 262), E3/3 (n = 710) = E2/4 (n = 30), E2/3 (n = 151), E2/2 (n = 6), LDL cholesterol decreased significantly in a stepwise manner. The decrease was not in a specific subgroup of LDL. In conclusion, for E2/2 subjects, lipoproteins isolated in the LDL density range appear to be composed mainly of dense IDL remnants and some Lp(a). The apo E isoform also has a significant effect on LDL concentration in both homozygotes and heterozygotes.

Original languageEnglish (US)
Pages (from-to)138-147
Number of pages10
JournalAtherosclerosis
Volume192
Issue number1
DOIs
StatePublished - May 2007

Bibliographical note

Funding Information:
This study was supported by National Institute of Health Grants DK02456, EDIC-NO1 DK62204 Epidemiology of Diabetes Interventions and Complications, the Juvenile Diabetes Foundation, the General Clinical Research Centers Program (MO1 RR0000037), National Center for Research Resources, the Clinical Nutrition Research Unit (DK35816) and contracts with the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health. We would like to thank the subjects of the DCCT/EDIC program and the investigators who participated in the study.

Keywords

  • Apo E genotype
  • E2/2
  • LDL
  • LDL composition
  • VLDL remnants

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