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      Plasma levels of apolipoprotein-E in residents of the European North of Russia

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          Abstract

          Background

          Apolipoprotein-E (apoE) is one of the metabolically active apoproteins and plays an important role in lipid metabolism. However, there are no data on levels of apoE in residents of the North in spite of the fact that specific features of lipid metabolism in the northerners are described. The present work was designed to study plasma levels of apoE in residents of the European North of Russia.

          Methods

          A total of 937 native residents of the European North of Russia (463 men and 474 women ) aged 13–60 years were included in the study. ApoE concentrations in the blood plasma were measured by immunoturbidimetric method.

          Results

          Plasma levels of apoE in residents of the European North of Russia were low. ApoE concentrations below the defined normal values were detected in 57.0% of the men and in 59.2% of the women. The mean plasma levels of apoE did not significantly differ in men and women (2.80 mg/dl vs 2.87 mg/dl). Plasma apoE concentrations in residents of the European North of Russia changed with age. Plasma levels of apoE decreased from 13 to 21 years in men and from 13 to 35 years in women and then increased in both sexes (p < 0.001).

          Conclusion

          The limits of variation of plasma apoE levels in residents of the European North of Russia shift towards lower values. Plasma levels of apoE below normal values were observed in approximately half of investigation subjects.

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          Most cited references48

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          Sex differences in lipid and lipoprotein metabolism: it's not just about sex hormones.

          It is commonly thought that sex hormones are important regulators of plasma lipid kinetics and are responsible for sexual dimorphism in the plasma lipid profile. Here we discuss the findings from studies evaluating lipid and lipoprotein kinetics in men and women in the context of what we know about the effects of exogenous sex hormone administration, and we conclude that it is more complicated than that. It has become clear that normal physiological alterations in the hormonal milieu (i.e. due to menopause or throughout the menstrual cycle) do not significantly affect plasma lipid homeostasis. Furthermore, parenterally administered estrogens have either no effect or only very small beneficial effects, whereas orally administered estrogens raise plasma triglyceride concentrations--a phenomenon that is not consistent with the observed sex differences and likely results from the hepatic "first-pass effect." The effects of progestogens and androgens mimic only in part the differences in plasma lipids between men and women. Thus, the underlying physiological modulators of plasma lipid metabolism responsible for the differences between men and women remain to be elucidated.
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            Plasma lipoproteins: apolipoprotein structure and function.

            Plasma lipoprotein metabolism is regulated and controlled by the specific apolipoprotein (apo-) constituents of the various lipoprotein classes. The major apolipoproteins include apoE, apoB, apoA-I, apoA-II, apoA-IV, apoC-I, apoC-II, and apoC-III. Specific apolipoproteins function in the regulation of lipoprotein metabolism through their involvement in the transport and redistribution of lipids among various cells and tissues, through their role as cofactors for enzymes of lipid metabolism, or through their maintenance of the structure of the lipoprotein particles. The primary structures of most of the apolipoproteins are now known, and various functional domains of these proteins are being mapped using selective chemical modification, synthetic peptides, and monoclonal antibodies. Furthermore, the establishment of structure-function relationships has been greatly advanced by the identification of genetically determined variants of specific apolipoproteins that are associated with a disorder of lipoprotein metabolism. Future studies will rely heavily on the use of recombinant DNA technology and site-specific mutagenesis to elucidate further the correlations between structure and function and the role of specific apolipoproteins in lipoprotein metabolism.
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              Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes.

              Type III hyperlipoproteinemia (HLP) is a genetic disorder characterized by accumulation of remnant lipoproteins in the plasma and development of premature atherosclerosis. Although receptor binding-defective forms of apolipoprotein (apo) E are the common denominator in this disorder, a number of apparent paradoxes concerning its pathogenesis still exist. However, studies in transgenic animals are resolving the mechanisms underlying this disorder. PARADOX I: Defective apoE (commonly apoE2) is essential but not sufficient to cause overt type III HLP. In fact, most apoE2 homozygotes are hypolipidemic. Studies in apoE2 transgenic models have demonstrated the impact of other genes or hormones in converting the hypolipidemia to hyperlipidemia. PARADOX II: Among apoE2 homozygotes, men are more susceptible than women to type III HLP. Transgenic studies have shown that estrogen affects both LDL receptor expression and lipolytic processing, explaining the resistance of women to this disorder until after menopause. PARADOX III: ApoE deficiency is associated with hypercholesterolemia, whereas the type III HLP phenotype is characterized by both hypercholesterolemia and hypertriglyceridemia. The hypercholesterolemia is caused by impaired receptor-mediated clearance, whereas the hypertriglyceridemia is caused primarily by impaired lipolytic processing of remnants and increased VLDL production associated with increased levels of apoE. PARADOX IV: ApoE2 is associated with recessive inheritance of this disorder, whereas other defective apoE variants are associated with dominant inheritance. Determinants of the mode of inheritance are the differential binding of apoE variants to the LDL receptor versus the HSPG/LRP complex and the preference of certain apoE variants for specific lipoproteins. Thus, the pathogenesis of this sometimes mysterious disorder has been clarified.
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                Author and article information

                Contributors
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central
                1476-511X
                2013
                27 March 2013
                : 12
                : 43
                Affiliations
                [1 ]Institute of Physiology, Komi Science Center, Ural Branch of Russian Academy of Sciences, Pervomaiskaya av. 50, Syktyvkar, 167982, Russia
                [2 ]Faculty of Health Sciences, University of Tromso, Tromso, Norge, NO-9037, Norway
                Article
                1476-511X-12-43
                10.1186/1476-511X-12-43
                3621782
                23537337
                33b24c5b-53ae-4085-bd3c-8798ae1f3096
                Copyright ©2013 Kaneva et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 January 2013
                : 21 March 2013
                Categories
                Research

                Biochemistry
                adaptation,age,apolipoprotein-e,lipid metabolism,the north
                Biochemistry
                adaptation, age, apolipoprotein-e, lipid metabolism, the north

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