Sex-Related Differences in the Phenotypic Expression of the Apolipoprotein A-IMilano Mutant

Lipoprotein(a) (Lp(a)) besteht aus einem LDL-Partikel, an dem über das Apolipoprotein B100 des Partikels eine Disulfidbrücke zu einem Apolipoprotein(a) besteht ( Abb. 1 ). Obwohl Lp(a) bereits 1963 von Berg et al. erstmals als „lipoprotein associated antigen“ entdeckt 1 und schon früh ein Zusammenhang mit kardiovaskulären Ereignissen diskutiert wurde 2, konnten diese Annahmen der klinischen Eigenschaften erst deutlich später im Rahmen von epidemiologischen Evaluationen bestätigt werden 3, 4. Ab einer Lp(a)-Konzentration von über 30 mg/dl (> 75 nmol/l) besteht ein nahezu linearer Zusammenhang zwischen dem Anstieg der Lp(a)-Konzentration und kardiovaskulären Ereignissen wie Myokardinfarkt und das Risiko für eine Aortenklappenstenose 3, 4.

Download Full-text

Apolipoprotein(a), Fibrinopeptide A and Carotid Atherosclerosis in Middle-Aged Men

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648915 ◽

1994 ◽

Vol 72 (04) ◽

pp. 563-566 ◽

Cited By ~ 16

Author(s):

Tuomo Rankinen ◽

Sari Väisänen ◽

Michele Mercuri ◽

Rainer Rauramaa

Keyword(s):

Risk Factors ◽

Cardiovascular Diseases ◽

Carotid Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Bifurcation ◽

Carotid Intima Media Thickness ◽

Fibrinopeptide A ◽

Carotid Imt ◽

Apolipoprotein A ◽

The Difference

SummaryThe association between apolipoprotein(a) [apo(a)], fibrinogen, fibrinopeptide A (FPA) and carotid intima-media thickness (IMT) was analyzed in Eastern Finnish men aged 50 to 60 years. Apo(a) correlated directly with carotid bifurcation (r = 0.26, p = 0.001), but not with common carotid IMT. Men in the lowest quartile of apo(a) had thinner (p = 0.013) IMT in bifurcation [1.59 mm (95% Cl 1.49; 1.68)] compared to the men in the highest [1.91 mm (95% Cl 1.73; 2.09)] apo(a) quartile. The difference remained (p=0.038) after adjusting for confounders. Plasma fibrinogen was not related to carotid IMT, whereas FPA correlated with common carotid (r = 0.21, p = 0.016) and carotid bifurcation (r = 0.21, p = 0.018) IMT. These associations abolished after adjusting for the confounders. The data suggest that apo(a) associate with carotid atherosclerosis independent of other risk factors for ischemic cardiovascular diseases.

Download Full-text

The Identification and Significance of a Thr→Pro Polymorphism in Kringle IV Type 8 of Apolipoprotein(a)

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656083 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0949-0954 ◽

Cited By ~ 8

Author(s):

J Prins ◽

F R Lues ◽

Y Y van der Hoek ◽

J J.P Kastelein ◽

B N Bouma ◽

...

Keyword(s):

Case Control Study ◽

Amino Acid Position ◽

Case Control ◽

Binding Studies ◽

Binding Characteristics ◽

Apolipoprotein A ◽

Significant Independent Risk Factor ◽

And Gender ◽

Control Study

SummaryElevated plasma levels of lipoprotein(a) [Lp(a)] represent a significant independent risk factor for the development of atherosclerosis. Interindividual levels of apo(a) vary over 1000-fold and are mainly due to inheritance that is linked to the locus of the apolipoprotein(a) [apo(a)] gene. The apo(a) gene encodes multiple repeats of a sequence exhibiting up to 85% DNA sequence homology with plasminogen kringle IV (K.IV), a lysine binding domain. In our search for sequence polymorphisms in the K.IV coding domain, we identified a polymorphism predicting a Thr→Pro substitution located at amino acid position 12 of kringle IV type 8 of apo(a). The functional and clinical significance of this polymorphism was analysed in a case-control study and by comparing the in vitro lysine binding characteristics of the two Lp(a) subtypes.The case-control study (involving 153 subjects having symptomatic atherosclerosis and 153 age and gender matched normolipidemic controls) revealed an overall allele frequency for the Thr12-→Pro substitution in kringle IV type 8 of 14% and a negative association between presence of the Pro12-subtype and symptomatic atherosclerosis (p <0.03). The in vitro lysine binding studies, using Lp(a) isolated from subjects homozygous for either Thr12 or Pro12 in K.IV type 8, revealed comparable lysine-Sepharose binding fractions for the two subtypes. The binding affinity (Kd) for immobilised plasmin degraded des- AA-fibrin (DesafibTM-X) was also comparable for the two subtypes, however a decreased maximal attainable binding (Bmax) for immobilised desafibTM-X was observed for the Pro12-subtype Lp(a).

Download Full-text