Early Expression of the Apolipoprotein (a) Gene: Relationships Between Infants' and Their Parents' Serum Apolipoprotein (a) Levels

PEDIATRICS ◽  
1992 ◽  
Vol 89 (3) ◽  
pp. 401-406 ◽  
Author(s):  
Xing L. Wang ◽  
David E. L. Wilcken ◽  
Nicholas P. B. Dudman

The serum concentration of apo(a), the unique apolipoprotein of lipoprotein (a), reflects serum lipoprotein (a) levels. High concentrations are associated with increased cardiovascular risk. Inasmuch as atherogenesis may begin in childhood, the early expression of the apo(a) gene and relationships between serum levels in infants and their parents were explored. Serum apo(a) and lipid profiles were measured in 51 infants when aged 8.5 ± 2 months. They were from among 1032 consecutively born babies in whom apo(a) levels had been measured on day 2 to 5. Levels in 18 infants were in the top 5% of the neonatal apo(a) distribution and in 33 from below the 95th percentile. Parental values were also assessed. Infants' apo(a) levels (n = 51) at the ages of 2 to 5 days and 8.5 ± 2.3 months were highly correlated (r .73, P < .0001) and increased from an initial median value of 48 U/L (range 1 to 462 U/L) to 100 U/L (5 to 969 U/L) at 8.5 months, and they were then not different from parental levels. Measurements at both times were closely correlated with parental levels. Regression coefficients between 8.5-month levels, and the levels of fathers, of mothers, and the average level of both parents were 0.439, 0.521 and 0.93, respectively (P < .0001 for each). It is concluded that the gene for the regulation of apo(a) is fully expressed before the age of 1 year. The apo(a) levels in infants during this time track closely and are predictive of parental values. These results are consistent with apo(a) contributing to that part of coronary risk associated with a positive family history, with implications for both future childhood screening and family-based coronary prevention.

1997 ◽  
Vol 76 (7) ◽  
pp. 625-628 ◽  
Author(s):  
Casper B. Leerink ◽  
Cynthia V. S. de Vries ◽  
Fiona R. M. van der Klis

1990 ◽  
Vol 36 (12) ◽  
pp. 2019-2026 ◽  
Author(s):  
J J Albers ◽  
S M Marcovina ◽  
M S Lodge

Abstract 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. Apolipoprotein(a) is formed by three different structural domains having high amino acid sequence homology with plasminogen. One of the domains, called kringle 4, is present in multiple copies, the number of which varies and is genetically determined. This accounts for the size heterogeneity of apolipoprotein(a) and thus of Lp(a). Because high concentrations of Lp(a) are associated with atherosclerotic cardiovascular and cerebrovascular disease and may inhibit fibrinolysis, interest in measuring Lp(a) has increased considerably, leading to a rapid development of commercially available immunoassays for the measurement of Lp(a) in human plasma. However, the immunochemical measurement of Lp(a) has several peculiar problems in addition to those encountered by the measurements of other apolipoproteins. The major problems that need to be carefully evaluated are (a) the structural complexity and heterogeneity of Lp(a), (b) the homology of apolipoprotein(a) with plasminogen, (c) the lack of standardization of the methods, and (d) the lack of a common means of expressing the Lp(a) values.


1997 ◽  
Vol 134 (1-2) ◽  
pp. 150
Author(s):  
Hiroshi Shimizu ◽  
Takahiro Taniguchi ◽  
Yoshio Fujioka ◽  
Satoru Kawasaki ◽  
Akihiko Oda ◽  
...  

1993 ◽  
Vol 39 (3) ◽  
pp. 503-508 ◽  
Author(s):  
P Gillery ◽  
P Arthuis ◽  
C Cuperlier ◽  
R Circaud

Abstract This nephelometric assay of serum lipoprotein(a) [Lp(a)] is characterized by the use of a specific antibody to generate a high rate of light-scatter formation and the elimination of nonspecific reactions from serum samples by diluting samples in phosphate-buffered saline containing polymer enhancer polyethylene glycol (PEG), 40 g/L, and detergent before the assay. We reacted 100 microL of sixfold-diluted serum in 500 microL of buffer containing PEG with 42 microL of pure polyclonal rabbit antiserum (Dakopatts) directed against human Lp(a) and monitored the reaction by rate nephelometry with the Array Protein System nephelometer (Beckman). The standard curve for the reaction was linear in the Lp(a) range 10-1280 mg/L; antigen excess occurred between 1300 and 1400 mg/L. Calibration was performed with serial dilutions of a standard serum. Precision studies showed within-run and between-run CVs of < 2.1% and 6.9%, respectively. The nephelometric results (y) for 100 serum samples were highly correlated with those obtained by radial immunodiffusion (x) calibrated with the same materials: y = 1.07 (+/- 0.03) x - 16.2 (+/- 8.1) mg/L (r = 0.974, P < 0.001). Storing serum for 3 weeks at 4 degrees C or 3 months at -80 degrees C did not affect the results.


1997 ◽  
Vol 136 (1) ◽  
pp. 87-91 ◽  
Author(s):  
Helga Lotz ◽  
Giovanni B Salabè

Abstract Conflicting results have been reported regarding serum lipoprotein(a) (Lp(a)) concentrations in patients with hypothyroidism. We addressed the question whether thyroid autoimmunity could be associated with elevated Lp(a) values independent of the thyroid status. Lp(a) was measured by ELISA in 30 males, 29 premenopausal and 30 postmenopausal females positive for thyroid peroxidase- and/or thyroglobulin-antibody (T-Abs) and normolipidemic, screened out respectively from 428 male donors, 162 premenopausal donors and 108 postmenopausal females; they were compared with 65 males, 72 premenopausal and 48 postmenopausal females, negative for thyroid antibodies, normolipidemic and matched for age. T-Abs-positive male donors showed serum Lp(a) concentrations significantly increased compared with males without T-Abs (mean 19·7 ± 15·9 vs 12·7 ± 17·5 mg/dl; median 17·0 vs 4·0 mg/dl; Mann Whitney U test: P = 0·0000). In premenopausal females no difference could be found between T-Abs-positive and T-Abs-negative subjects (mean 13·2 ± 16·1 vs 12·3 ± 13·9 mg/dl; median 5·2 vs 8·7 mg/dl), suggesting an Lp(a) lowering effect of estrogens. The study was, therefore, extended to postmenopausal females. Significantly elevated Lp(a) levels were found in 30 postmenopausal females with T-Abs when compared with 48 postmenopausal females without T-Abs (40·0 ± 34·2 mg/dl vs 20·7 ± 19·3 mg/dl; median 32·0 vs 18·0 mg/dl; Mann Whitney U test: P = 0·0002). Finally, 21 postmenopausal, normolipidemic, autoimmune hypothyroid patients on l-thyroxine and euthyroid compared with 48 postmenopausal females without T-Abs also showed increased serum levels of Lp(a) (mean 27·0 ± 16·8 mg/dl vs 20·7 ± 19·3 mg/dl, median 25·0 vs 18 mg/dl; Mann Whitney U test: P = 0·0024). Thyrotropin levels in all subjects and patients were within the normal range. In conclusion, our results in males and postmenopausal females with T-Abs and euthyroid show an association between thyroid autoimmunity and increased levels of Lp(a), while the results obtained in premenopausal females suggest that estrogens might interfere with the Lp(a) increase related to thyroid autoimmunity. European Journal of Endocrinology 136 87–91


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