Antigens, Neoplasm ; genetics ; Apoprotein(a) ; genetics ; Carrier Proteins ; genetics ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Membrane Proteins ; genetics ; Mutation, Missense ; genetics ; Nuclear Proteins ; genetics ; Ovarian Neoplasms ; metabolism ; pathology ; Proprotein Convertase 5 ; genetics ; Salivary Cystatins ; genetics ; Ubiquitin-Protein Ligases ; genetics ; Whole Exome Sequencing

OBJECTIVETo investigate changes of serum total oxidation status (TOS) and total antioxidant status (TAS) and their association with apolipoprotein (a) [Apo(a)] in patients with polycystic ovary syndrome (PCOS) combined with infertility.

MWTHODSNinety patients with PCOS and infertility were selected as the study group, including 45 patients treated with antioxidants combined with Diane-35(group A) and 45 with Diane-35 therapy only (group B), with 45 healthy volunteers with normal menstruation and normal dual phase basic body temperatures as the control group. Serum TOS of the participants was determined by dual xylenol orange method, and serum TAS was determined with ABTS method; plasma Apo(a) level was determined by dual wavelength immune transmission turbidity method.

RESULTSBefore treatment, serum TOS, OSI, and Apo(a) levels were significantly higher and TAS level was significantly lower in the study group than in the control group (P<0.05). Serum TOS, OSI, and Apo (a) were significantly lowered and TAS was significantly increased in group A after the therapy as compared with the levels before therapy and the levels in group B. The rate of natural recovery of menstruation was significantly higher and the incidence of cardiovascular disease was significantly lower in group A than in group B (P<0.05). Pearson correlation analysis showed that serum TOS and OSI were positively correlated with plasma Apo(a) (r=0.524 and 0.531, P<0.05), and serum TAS was negatively correlated with plasma Apo(a) (r=-0.519, P<0.05).

CONCLUSIONAntioxidant therapy can lower TOS, OSI and Apo(a) levels and increase TAS level to lessen oxidative stress, improve the prognosis, and reduce the risks of cardiovascular disease in patients with PCOS and infertility.

Antioxidants ; metabolism ; Apoprotein(a) ; blood ; Cyproterone Acetate ; therapeutic use ; Drug Combinations ; Ethinyl Estradiol ; therapeutic use ; Female ; Humans ; Infertility, Female ; blood ; Oxidative Stress ; Polycystic Ovary Syndrome ; blood ; drug therapy

Human apolipoprotein (a) (LPA) gene is highly polymorphic, and the polymorphic loci on this gene include the Kringle 4 subtype 2(KIV-2) repeat polymorphism, the pentanucleotide repeat (TTTTA)n polymorphism, and a number of single nucleotide polymorphisms. KIV-2 repeat polymorphism was found to be significantly associated with coronary heart disease(CHD), and the reducing number of KIV-2 repeats is a risk factor for CHD. Both the increase and decrease of the pentanucleotide repeat(TTTTA)n polymorphism repeats are possibly associated with CHD risk. In single nucleotide polymorphisms loci, the rs10455872 and rs3798220 loci were widely reported to be associated with CHD, while other loci were less reported. The association between LPA polymorphisms and CHD may be mediated by either the elevation of plasma LPA level or the change of LPA subtypes. This article reviews the association between the LPA polymorphisms and CHD and the underlying mechanisms.
Apoprotein(a) ; Coronary Artery Disease ; Humans ; Microsatellite Repeats ; Polymorphism, Single Nucleotide ; Risk Factors

OBJECTIVETo assess the atherogenicity of lipoprotein(a), the effect of the heterogeneity of lysine binding of apolipoprotein(a) [apo(a)], a plasminogen-like glycoprotein component on the proliferation of human arterial smooth muscle cells (SMCs).

METHODSBoth wild type (wt) Trp72 and mutant (mut) Trp72-->Arg forms of apo(a) kringle IV-10 were expressed by employing a GST-gene fusion system into E. coli. The proliferation of SMCs was determined by flow cytometry and MTT colorimetry. Enzyme-linked immunosorbent assay (ELISA) assay was used to detect the active form of transforming growth factor beta(1) (TGF-beta(1)).

RESULTSApo(a) wt-kringle IV-10 that has lysine binding properties possessed a growth-stimulating activity to SMCs on a dose-dependence manner by stimulating cells in the G(1)/G(0) phase of cell cycle to S and G(2)/M phase, and reduced significantly the amounts of endogenous active TGF-beta(1) in culture when compared with the control medium and the GST group (2.4 +/- 0.5 vs 8.6 +/- 1.6 and 9.1 +/- 1.7 ng/ml, P < 0.01). The growth-stimulating effect of apo(a) mut-kringle IV-10 deficient in lysine binding was negligible.

CONCLUSIONSApo(a) induces SMCs growth by inhibiting the activation of latent TGF-beta(1), an activity that may involve the ability of apo(a) kringle IV-10 to bind lysine. The mitogenic effect of apo(a) wt-kringle IV-10 on SMCs might play an active role in the atherogenic function of lipoprotein(a).

Apolipoproteins ; genetics ; metabolism ; Apoprotein(a) ; Cell Division ; physiology ; Humans ; In Vitro Techniques ; Kringles ; genetics ; Lipoprotein(a) ; genetics ; metabolism ; Muscle, Smooth, Vascular ; cytology ; Transforming Growth Factor beta ; metabolism

BACKGROUND: The structure of lipoprotein(a) [Lp(a)] includes a low-density lipoprotein cholesterol (LDL-C) component and apolipoprotein(a) [apo(a)] linked to apolipoprotein B-100 of LDL-C with a disulfide bond. Liver cirrhosis is the only disease in which the decrease of serum Lp(a) concentra-tion is observed as a secondary effect. In this study, we tried to investigate the mechanisms for the Lp(a) decrease in cirrhotic patients. METHODS: Forty Child 's class A cirrhotic patients, 40 Child 's class C patients from Asan Medical Center, and 80 healthy controls were recruited. Serum concentrations of interleukin-6 (IL-6), LDL-C, Lp(a), and free apo(a) were measured. RESULTS: The serum concentrations of Lp(a) in the Child 's class C patients were significantly lower than those in class A and the control group (P < 0.05). The apo(a) concentrations in the Child 's class C patients were significantly lower than those in class A and the control group (P < 0.05). The LDL-C concentrations of Child 's class C patients were significantly lower than those in class A and the con-trol group (P < 0.01). The IL-6 concentrations of Child 's class C patients were significantly higher than those in class A and the control group (P < 0.005). Serum concentrations of Lp(a) showed positive correlations with those of LDL-C (r=0.42, P < 0.0001) and with those of the free apo(a) (r=0.68, P < 0.0001). But serum concentrations of IL-6 had no correlation to those of the Lp(a) or the free apo(a). CONCLUSIONS: Considering the positive correlation between Lp(a) and LDL-C, the decrease in the serum Lp(a) in cirrhotic patients could be due mainly to the decrease in the LDL component, although we could not suggest the mechanism for the LDL decrease.
Apolipoprotein B-100 ; Apolipoproteins* ; Apoprotein(a)* ; Child ; Cholesterol ; Cholesterol, LDL* ; Chungcheongnam-do ; Humans ; Interleukin-6 ; Lipoprotein(a)* ; Lipoproteins* ; Liver Cirrhosis* ; Liver*

OBJECTIVEThis study inquired into the relationship between a pentanucleotide repeats(PNR) polymorphism of the apolipoprotein(a)[apo(a)] gene and coronary atherosclerotic heart disease(CHD) in Chinese Han nationality.

METHODSPNR polymorphism of the apo(a) gene from 165 cases of CHD and 153 normal individuals were analyzed by polymerase chain reaction(PCR)-denature polyacrylamide gel electrophoresis-silver stain.

RESULTSThe frequencies of (TTTTA)(5/8) genotype (0.188) and (TTTTA)(5) allele (0.115) in CHD group were remarkably higher than those in control group (0.039, 0.026)(P<0.01, P<0.05).

CONCLUSIONThese findings indicate that the PNR polymorphism of apo(a) is associated with the susceptibility to CHD, which may be involved in the development of CHD.

Aged ; Apolipoproteins ; genetics ; Apoprotein(a) ; Asian Continental Ancestry Group ; genetics ; Coronary Artery Disease ; genetics ; Coronary Disease ; genetics ; Electrophoresis, Polyacrylamide Gel ; methods ; Female ; Gene Frequency ; Humans ; Lipoprotein(a) ; genetics ; Male ; Microsatellite Repeats ; genetics ; Middle Aged ; Oligonucleotides ; genetics ; Polymerase Chain Reaction ; methods ; Polymorphism, Genetic

BACKGROUND: Lipoprotein (a) [Lp(a)] contains apolipoprotein(a), which is a structural homologue of plasminogen and competes with it for binding sites. It also acts by increasing plasminogen activator inhibitor-1 expression. The objective of this study was to evaluate the relationship between Lp(a) levels and restenosis rate after successful coronary stent placement. METHODS: The study included 306 patients who underwent coronary stent placement and follow-up coronary angiogram at Chonnam National University Hospital from August 1996 to June 2000. Restenosis rate was analyzed according to the level of Lp(a); Group I with high Lp(a) (n=7, Lp(a) 36 mg/dL, 58.98.8 years, female: 35.1%) and Group II with low Lp(a) (n=29, Lp(a) < 36 mg/dL, 57.79.8 years, female: 18.8%). RESULTS: 1) There was no significant differences in risk factors of atherosclerosis, clinical diagnosis, the number of involved coronary artery, left ventricular function, angiographic lesion characteristics by American College of Cardiology/American Heart Association clasification and Thrombolysis In Myocardial Infarction flow in two groups. 2) Angiographic restenosis rates were not different between two groups (group I : 33.8%, group II : 35.4%). CONCLUSION: Plasma Lp(a) levels are not related with the angiographic restenosis rate after coronary stent placement.
Apoprotein(a) ; Atherosclerosis ; Binding Sites ; Coronary Vessels ; Diagnosis ; Female ; Follow-Up Studies ; Heart ; Humans ; Jeollanam-do ; Lipoprotein(a)* ; Myocardial Infarction ; Plasma ; Plasminogen ; Plasminogen Activators ; Risk Factors ; Stents* ; Ventricular Function, Left

BACKGROUND: Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein that is assembled from a low density lipoprotein(LDL) and apolipoprotein(a) [apo(a)]. The variations in Lp(a) concentration tend to be inversely related to the number of kringle IV in apo(a) gene, but other polymorphisms [pentanucleotide(TTTTA) repeats, +93 C/T polymorphism, and Met/Thr polymorphism] of the apo(a) gene are also seems to be related to Lp(a) concentrations. The purpose of this study was to investigate the association of the pentanucleotide repeat polymorphism(PNRP) and Met/Thr polymorphism with the Lp(a) concentrations. METHODS: We studied 197 healthy adults. For genotype analysis of the PNRP and the Met/Thr polymorphism, PCR was performed. Apo(a) phenotyping was performed by SDS-PAGE and immunoblotting. The Lp(a) concentrations were measured by ELISA method. More than two groups were compared using the Kruskal Wallis one-way analysis test. To establish a relationship between gene polymorphisms and Lp(a) concentrations, The linear regression test was performed. RESULTS: Mean Lp(a) concentration was 25.3+/-21.5 mg/dL. Allele frequencies for PNRP, subjects with 8/8 genotype were 114(57.9%) and most frequently observed. The Lp(a) concentrations showed the tendency to decrease as the sum of alleles of PNR increased. Subjects with Met/Thr genotype were 119(60.4%), Met/Met genotype were 71(36.0%) and Thr/Thr genotype were 7(3.6%). CONCLUSIONS: For PNRP, subjects with 8/8 genotype were 114(57.9%) and 8/8 genotype was the most frequently observed. Met/Thr genotype was most frequently observed.
Adult ; Alleles* ; Apoprotein(a) ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Gene Frequency* ; Genotype ; Humans ; Immunoblotting ; Kringles ; Linear Models ; Lipoprotein(a) ; Lipoproteins ; Microsatellite Repeats ; Polymerase Chain Reaction

Lp(a) is an independent risk factor of atherosclerotic cardiovascular diseases. Marked increase in plasma lipoprotein(a)[Lp(a)] was reported in conti- nuous ambulatory peritoneal dialysis(CAPD) patients. Serum albumin, parameters of nutritional status and parameters of dialysis have been reported to be related with Lp(a) concentration. Eighty nine patients(age 52 +/- 13, M: F 61: 28) undergoing CAPD were included in this study. We measured Lp(a) concentration, apolipoprotein(a) [apo(a)] phenotype, serum albumin, parathyroid hormone (PTH), Creactive protein(CRP), fibrinogen, 24 hour peritosol protein ancl albumin, 24 hour urine protein and albumin, total albumin clearance, residual renal function(RRF), and parameters of nutritional status such as prealbumin, triceps skin fold(TSF), mid-arm muscle area(MAMA), and normalized protein cata- bolic rate(nPCR). Peritoneal equilibration test(PET) and weekly Kt/V,. were also measured to evaluate relationship of Lp(a) and the adequacy of dialysis. The median serum Lp(a) was 48.9mg/dl(29.1-73.5 mg/dl) (quartiles). Higher Lp(a) level was observed in the low molecular weight apo(a) subgroup. There was no significant difference in serum Lp(a) levels between male and female, diabetic and non-diabetic patients, smokers and non-smokers. Serum albumin was negatively correlated(r=-0.28, p<0.01), while total albumin clearance was positively correlated with Lp (a)(r=0.20, p<0.05). 4)gLp(a) was not correlated with age, duration of dialysis, prealbumin, fibrinogen, RRF, weekly Kt/V, PET, PTH, CRP, TSF, MAMA, nPCR, 24hour peritosol protein and albumin and 24hour urine protein and albumin. Multivariate analysis using apo(a) phenotype, serurn albumin, total albumin clearance as independent variables revealed that serum albumin and apo(a) phenotype were significantly related with logLp(a)(p<0.05). Apo(a) phenotype and serum albumin were the factors that were independently associated with se- rum Lp(a) concentration in CAPD patients.
Apoprotein(a) ; Cardiovascular Diseases ; Dialysis ; Female ; Fibrinogen ; Humans ; Lipoprotein(a)* ; Male ; Molecular Weight ; Multivariate Analysis* ; Nutritional Status ; Parathyroid Hormone ; Peritoneal Dialysis, Continuous Ambulatory* ; Phenotype ; Plasma ; Prealbumin ; Risk Factors ; Serum Albumin ; Skin

Lipoprotein(a)[Lp(a)] represents a class of lipoprotein particles defined by the presence of apolipoprotein(a), a unique glycoprotein linked by a disulfide bond to apolipoprotein B-100 to form a single macromolecule. It was known that Lp(a) levels were associated with risk factor for cardiovascular disease and were fluctuated during pregnancy and postpartum. In the present study, plasma Lp(a) levels were estimated in two groups of women comprising 48 normal spontaneous vaginal delivery group and 52 Cesarean section delivery group. The changes of plasma Lp(a) concentrations were serially estimated before delivery, postpartum 1 weeks and postpartum 6 weeks. The result can be summarized as follows.1. Mean ploasma Lp(a) levels were changed from 43.9 +/- 28.4 mg/dl at delivery to 68.5 +/- 35.5 mg/dl at postpartum 1 weeks 73.1 +/- 35.7 mg/dl versus 63.7 +/- 35.1 mg/dl. And after postpartum 6 weeks, mean plasma Lp(a) levels were returned to near initial levels 48.4 +/- 21.1 mg/dl versus 42.2 +/- 16.7 mg/dl.3. Lp(a) levels were significantly rised postpartum 1 weeks compared with before delivery(p < 0.05) and after postpatum 6 weeks(p < 0.05). In conclusion, serum Lp(a) levels were increased postpartum 1 weeks with significant value, and returned to initial levels after postpartum 6 weeks. Our findings suggests that Lp(a) has the characteristics of an acute phase reactant rather modulated by endogenous hormone.
Apolipoprotein B-100 ; Apoprotein(a) ; Cardiovascular Diseases ; Cesarean Section ; Female ; Glycoproteins ; Humans ; Lipoprotein(a)* ; Lipoproteins ; Plasma* ; Postpartum Period* ; Pregnancy ; Risk Factors