Association of Polymorphisms of the Apolipoprotein(a) Gene With Lipoprotein(a) Levels and Myocardial Infarction

Holmer, Stephan; Hengstenberg, Christian; Kraft, H. G.; Mayer, Björn; Pöll, Melanie; Kürzinger, Susanne; Fischer, Marcus; Löwel, Hannelore; Klein, G.; Riegger, Günter A.J.; Schunkert, Heribert

doi:10.1161/01.cir.0000048125.79640.77

Cited by 72 publications

(35 citation statements)

References 42 publications

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“…However, the KIV-2 CNV alone explains only a considerably smaller fraction (19-77%) of the variation in Lp(a) concentrations depending on the population and methods used (35,36,173,177). Many studies aimed at identifying sequence variation in the LPA gene, other than the KIV-2 size polymorphism, have been conducted in an effort to explain the fraction of variation in Lp(a) plasma concentrations not explained by the KIV-2 CNV.…”

Section: Sequence Variation In Lpa Affecting Lp(a) Levelsmentioning

confidence: 99%

Structure, function, and genetics of lipoprotein (a)

Schmidt

Noureen

Kronenberg

et al. 2016

Journal of Lipid Research

444

346

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between apoB-100 of the LDL moiety and one of the kringle domains in apo(a) (4,5,(14)(15)(16). The assembly of Lp(a) is believed to occur at the hepatocyte cell membrane surface (17), but other scenarios have also been proposed [reviewed in (18, 19)].Lp(a) was originally described as a dichotomous (Lp+, Lp) genetic trait (20), but it soon became evident that it is quantitative rather than qualitative in nature (21-23). Lp(a) plasma concentrations are highly heritable (24-28). The major locus controlling the Lp(a) concentrations is the LPA gene (MIM 152200; ENSG00000198670) on the reverse strand of chromosome 6q27 (29-31), which encodes the apo(a) component of Lp(a) (25,26,(32)(33)(34). Close LPA orthologs are found in all apes and in Old World monkeys. INTRA-AND INTER-POPULATION DIFFERENCES INLp ( INTRODUCTION TO THE LIPOPROTEIN (a) TRAITHuman lipoprotein (a) [Lp(a)] is a macromolecular complex in plasma that was first described in 1963 by the Norwegian physician Kåre Berg (1). Ever since its discovery, this enigmatic particle has intrigued basic researchers and clinicians due to its unknown physiological function and its association with atherosclerotic diseases, in particular coronary heart disease (CHD) [reviewed in (2)]. Lp(a) is composed of one molecule of a LDL-particle containing apoB-100 and one molecule of a large highly polymorphic glycoprotein named apo(a) (3-6). A characteristic feature of apo(a) is the presence of loop-like structures called kringles (7,8). Kringle domains are triple loop structures stabilized by three internal disulfide bonds and are also present in other coagulation factors, such as plasminogen (PLG), prothrombin, urokinase, and tissue-type PLG activators (9-12). In contrast to PLG, the linker domain between kringles is glycosylated in apo(a). The apo(a) is synthesized by the liver (13). The two components of Lp(a) are covalently linked together by a disulfide bond

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Section: Sequence Variation In Lpa Affecting Lp(a) Levelsmentioning

confidence: 99%

Structure, function, and genetics of lipoprotein (a)

Schmidt

Noureen

Kronenberg

et al. 2016

Journal of Lipid Research

444

346

View full text Add to dashboard Cite

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“…DNA-based tests that distinguish the various apo(a) alleles according to haplotype could be developed to reliably predict Lp(a) levels. 17 Several genetic variations clearly influence CHD through mechanisms that are independent of traditional risk factors, although they may not be independent of markers of inflammation such as C-reactive protein or myeloperoxidase. The recently reported myocyte enhancer factor 2A variation is highly penetrant, although its frequency in the population is probably low.…”

Section: Multilocus Testingmentioning

confidence: 99%

Genetic Basis of Atherosclerosis: Part II

2004

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“…However, discordant results have been reported concerning the contribution of apo(a) size to CHD risk independent of Lp(a) concentrations (3,4,(11)(12)(13)(14)(15)(16)(17)(18). Substantial methodologic variation in determining Lp(a) concentrations and apo(a) size may explain the difference in findings.…”

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confidence: 94%