Apolipoprotein polymorphisms and familial hypercholesterolemia

University of Athens, Laboratory of Molecular Genetics, Department of Nutrition and Dietetics, Harokopio, 70 El. Venizelou Str, 17671 Kallithea-Athens, Greece.
Pharmacogenomics (Impact Factor: 3.22). 10/2007; 8(9):1179-89. DOI: 10.2217/14622416.8.9.1179
Source: PubMed


The majority of apolipoproteins known to play a major role in lipid metabolism were identified over 20 years ago, and nine of them (APOA1, -A2, -A4, -B48, -B100, -C1, -C2, -C3 and -E) have long been known to be most relevant to the regulation of lipoproteins. Polymorphisms of genes encoding apolipoproteins influence plasma levels of high-density lipoproteins (HDL), very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) chylomicrons or triglycerides. Familial hypercholesterolemia (FH), an autosomal dominant disorder, is caused by mutations mainly located in the low-density lipoprotein receptor (LDLR) gene, or more rarely within the apolipoprotein B-100 gene or the gene encoding a secreted proteinase PSCK9. FH is characterized by elevated concentrations of LDL, deposition of LDL-derived cholesterol in tendons, skin xanthomas, and premature coronary artery disease. The frequency of heterozygotes is approximately one in 500 persons, placing FH among the most common inborn errors of metabolism. The risk of cardiovascular disease in these patients is influenced not only by the type of the mutations they carry, but also by the haplotype of lipid modifier genes, as is the case of apolipoproteins. In this review, we present current information that demonstrates the impact of apolipoprotein polymorphisms on the FH phenotype.

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    • "A naszcens kilomikron A (I–II–IV–V) és B48 típusú apolipoproteineket tartalmaz [5] [6] "
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    ABSTRACT: Elevated plasma lipid level is one of the main risk factors for cardiovascular diseases, which are considered to be pimary causes of death. Apolipoprotein E plays a part in the lipid transport in the blood, thus polimophisms of that affect the lipid composition of the plasma. The three most common alleles of apolipoprotein E are e2, e3, e4. Out of the two non-wild type alleles, the e2 and e4, the latter was shown to play a role in the development of cardiovascular diseases and Alzheimer's disease. Some studies mention the e2/e2 homozygote genotype as one of the causes of hyperlipoproteinemia type III. Besides lipid metabolism, apolipoprotein E also influences the manifestation of cardiovascular diseases through other biochemical pathways, therefore it is essential to explore the molecular background of these metabolic pathways. Orv. Hetil., 2012, 153, 2070-2076.
    Orvosi Hetilap 12/2012; 153(52):2070-2076. DOI:10.1556/OH.2012.29508
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    • "While environmental factors, such as diet, are important determinants of circulating lipid concentrations, heritabilities of lipid profiles have been well elucidated in twin studies [3–6]. Because of the well-established association between circulating cholesterol levels and cardiovascular diseases, genes involved in cholesterol synthesis and transport have been more extensively studied than the others involved in long-chain fatty acids (LCFAs) and phospholipids [2, 7–11]. "
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    ABSTRACT: Dysfunctional lipid metabolism plays a central role in pathogenesis of major chronic diseases, and genetic factors are important determinants of individual lipid profiles. We analyzed the associations of two well-established functional polymorphisms (FABP2 A54T and APOE isoforms) with past and family histories of 1492 population samples. FABP2-T54 allele was associated with an increased risk of past history of myocardial infarction (odds ratio (OR) = 1.51). Likewise, the subjects with APOE4, compared with E2 and E3, had a significantly increased risk of past history myocardial infarction (OR = 1.89). The OR associated with APOE4 was specifically increased in women for past history of myocardial infarction but decreased for gallstone disease. Interactions between gender and APOE isoforms were also significant or marginally significant for these two conditions. FABP2-T54 allele may be a potential genetic marker for myocardial infarction, and APOE4 may exert sex-dependent effects on myocardial infarction and gallbladder disease.
    Cholesterol 09/2011; 2011(10):896360. DOI:10.1155/2011/896360
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    • "The type of LDLR mutation has been shown to correlate with the response to statin therapy [46]. Polymorphisms in lipid modifier genes, such as apolipoproteins, particularly ApoE, can significantly affect the FH phenotype [47]. Conventional risk factors for atherosclerosis such as smoking, diet, hypertension, and diabetes are also additive in FH [48,49]. "
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    ABSTRACT: Familial Hypercholesterolemia (FH) is a common cause of premature cardiovascular disease and is often undiagnosed in young people. Although the disease is diagnosed clinically by high LDL cholesterol levels and family history, to date there are no single internationally accepted criteria for the diagnosis of FH. Several genes have been shown to be involved in FH; yet determining the implications of the different mutations on the phenotype remains a hard task. The polygenetic nature of FH is being enhanced by the discovery of new genes that serve as modifiers. Nevertheless, the picture is still unclear and many unknown genes contributing to the phenotype are most likely involved. Because of this evolving polygenetic nature, the diagnosis of FH by genetic testing is hampered by its cost and effectiveness. In this review, we reconsider the clinical versus genetic nomenclature of FH in the literature. After we describe each of the genetic causes of FH, we summarize the known correlation with phenotypic measures so far for each genetic defect. We then discuss studies from different populations on the genetic and clinical diagnoses of FH to draw helpful conclusions on cost-effectiveness and suggestions for diagnosis.
    Nutrition & Metabolism 04/2011; 8(1):23. DOI:10.1186/1743-7075-8-23 · 3.26 Impact Factor
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