Lipoprotein (a): impact by ethnicity and environmental and medical conditions

Enkhmaa, Byambaa; Anuurad, Erdembileg; Berglund, Lars

doi:10.1194/jlr.r051904

Cited by 190 publications

(160 citation statements)

References 237 publications

(234 reference statements)

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“…3). A further discussion of apo(a) in different ethnic groups can be found in this Thematic Review series (136). KIV-2 sizes (156,157), possibly indicating that size changes in the KIV-2 CNV are mostly of comparatively restricted magnitude per mutation event.…”

Section: Genetic Polymorphisms Within Lpamentioning

confidence: 80%

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Structure, function, and genetics of lipoprotein (a)

Schmidt

Noureen

Kronenberg

et al. 2016

Journal of Lipid Research

443

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: Genetic Polymorphisms Within Lpamentioning

confidence: 80%

“…In these individuals, the CNV genotype can also be directly deduced from the phenotype. However, the frequencies of double band phenotypes reported in the literature vary considerably and range from 30 to 90% [see (136) in this Thematic Review series]. The reason for this is twofold.…”

Section: Downloaded Frommentioning

confidence: 99%

Structure, function, and genetics of lipoprotein (a)

Schmidt

Noureen

Kronenberg

et al. 2016

Journal of Lipid Research

443

346

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“…Concentrations also differ between different ethnicities, with higher concentrations in individuals of African compared with European and Asian descent (14,(68)(69)(70)(71)(72)(73)(74). In Europeans and Asians, Lp(a) concentrations are highly skewed with a tail toward higher concentrations (Fig.…”

Section: Plasma Concentrations and Geneticsmentioning

confidence: 99%

Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology

Nordestgaard

Langsted

2016

Journal of Lipid Research

440

262

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“…Physiologic, dietary and environmental factors play a relatively minor role and can either lower or raise Lp(a) plasma levels. 5 Furthermore, it is well appreciated that significant ethnic differences exist in Lp(a) levels, with highest levels present in subjects of African descent and generally followed in decreasing order of lower levels in southern Asians, Whites, Hispanics and east Asians. 2,6,7 …”

Section: Introductionmentioning

confidence: 99%

LPA Gene, Ethnicity, and Cardiovascular Events

et al. 2017

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Background The relationship of LPA single nucleotide polymorphisms (SNPs), apolipoprotein(a) isoforms and lipoprotein(a) [Lp(a)] levels with major adverse cardiovascular (MACE) events in different ethnic groups is not well known. Methods LPA SNPs, apolipoprotein(a) isoforms, Lp(a) and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) levels were measured in 1792 Black, 1030 White and 597 Hispanic subjects enrolled in the Dallas Heart Study. Their interdependent relationships and prospective association with MACE after median 9.5-year follow-up were determined. Results LPA SNP rs3798220 was most prevalent in Hispanics (42.38%), rs10455872 in Whites (14.27%) and rs9457951 in Blacks (32.927%). The correlation of each of these SNPs with the major apolipoprotein(a) isoform size was highly variable and in different directions among ethnic groups. In the entire cohort, Cox regression analysis with multivariable adjustment revealed that quartiles 4 of Lp(a) and OxPL-apoB were associated with hazard ratios (HR) (95% CI) for time to MACE of 2.35 (1.50-3.69), p<0.001) and 1.89 (1.26-2.84), p=0.003), respectively, versus quartile 1. Addition of the major apolipoprotein(a) isoform and the 3 LPA SNPs to these models attenuated the risk, but significance was maintained for both Lp(a) and OxPL-apoB. Evaluating specific ethnic groups, in Blacks Lp(a) was a positive predictor and the size of the major apolipoprotein(a) isoform and inverse predictor, in Whites the size of the major apolipoprotein(a) isoform was an inverse predictor and in Hispanics OxPL-apoB was a predictor of time to MACE. Conclusion The prevalence and association of LPA SNPs with size of apolipoprotein(a) isoforms, Lp(a) and OxPL-apoB levels are highly variable and ethnicity-specific. The relationship to MACE is best explained by elevated plasma Lp(a) or OxPL-apoB levels, despite significant ethnic differences in LPA genetic markers.

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Lipoprotein (a): impact by ethnicity and environmental and medical conditions

Cited by 190 publications

References 237 publications

Structure, function, and genetics of lipoprotein (a)

Structure, function, and genetics of lipoprotein (a)

Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology

LPA Gene, Ethnicity, and Cardiovascular Events

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