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W Patsch

Publications and source records attributed to W Patsch.

At least 19 recordsLinked to original sources
PubMed1992

Short-term intraindividual variability in lipoprotein measurements: the Atherosclerosis Risk in Communities (ARIC) Study.

Much epidemiologic research is based on estimation of an association between a putative risk factor and a health outcome--for example, plasma concentration of lipoproteins and ischemic heart disease. Since the repeatability of a risk factor measurement determines, in part, the ability to ascertain its association in populations, the Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability Study was conducted to estimate various components of variation in analyte data and to estimate the repeatability of these measurements. A total of 40 subjects (17 males and 23 females) from Forsyth County, North Carolina, Minneapolis, Minnesota, Jackson, Mississippi, and Washington County, Maryland, were studied in 1988. Fasting blood was collected three times from each subject, with a 1- to 2-week interval between each visit. The contributions of between-person variability, within-person variability, and processing and assay variability were estimated. From these components, the reliability coefficient, R, the correlation between measures made at repeat visits, was estimated. R was above 0.85 for total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and lipoprotein(a). Low repeatability was obtained for apolipoprotein A-I (R = 0.60). High density lipoprotein subfractions 2 and 3 were intermediate in repeatability. Reliability coefficients from the ARIC Intraindividual Variability Study are generally higher than those found in other studies, and this is related to relative variability in populations studied, to the time between measurements, and to differences in laboratory variability. Only for apolipoprotein A-I would the findings strongly suggest the need to adjust for measurement variability in estimation using one of these analytes as an independent variable.

Cardiovascular Diseases↗
PubMed1992

Postprandial lipemia: reliability in an epidemiologic field study.

Ten subjects from the Forsyth County, North Carolina, and Washington County, Maryland, field centers in the Atherosclerosis Risk in Communities Study had two fat tolerance tests within a 10-day period from September 1988 to February 1989 to determine the reproducibility of markers for postprandial lipemia. No significant differences between visits were found in fasting mean plasma lipids, lipoproteins, and apolipoproteins. Postprandial triglycerides and retinyl palmitate were measured at 3.5 and 9.0 hours after the test meal in whole plasma. There were no significant differences in the mean levels of these analytes between visits. The correlation of triglycerides between repeat visits at 9.0 hours (r = 0.87) was stronger than in fasting samples (r = 0.67) or at 3.5 hours (r = 0.69). The mean plasma retinyl palmitate level at 3.5 hours was 15% higher than at the 9.0-hour level. The correlation of repeat measures of retinyl palmitate at 9.0 hours (r = 0.94) was much stronger than at 3.5 hours (r = 0.79). In conclusion, estimates of reliability in postprandial measurements of 9.0-hour triglycerides and retinyl palmitate levels were as strong as fasting lipid measurements of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol, and both postprandial triglyceride measurements exceeded that of fasting triglyceride (r = 0.67).

Apolipoproteins↗
PubMed1992

The relation of high density lipoprotein cholesterol and its subfractions to apolipoprotein A-I and fasting triglycerides: the role of environmental factors. The Atherosclerosis Risk in Communities (ARIC) Study.

Cross-sectional analysis of four general representative populations of middle-aged adults in the United States in 1986-1989 provides estimates of the close relation of high density lipoprotein cholesterol (HDL cholesterol) to its major structural apolipoprotein (apolipoprotein A-I) and to fasting plasma triglyceride levels. HDL cholesterol differences of approximately 0.4 mg were associated with 1-mg differences in apolipoprotein A-I; differences of 20% in HDL cholesterol (reductions) were associated with triglyceride doublings. Variation in apolipoprotein A-I and triglyceride concentration together accounted for 66% of the population variance in HDL cholesterol. The uniformity of this pattern in the four race-sex groups studied suggests an important role of triglyceride-cholesterol transfer as a determinant of HDL cholesterol. The fundamental relations observed among HDL cholesterol, apolipoprotein A-I, and triglycerides were unaltered by levels of factors under personal volition. The volitional factors appeared to influence HDL cholesterol indirectly: Obesity and physical activity were affected primarily through their associations with triglycerides, and alcohol use and smoking through associations with apolipoprotein A-I. The association of alcohol use with elevated HDL cholesterol was attenuated in persons with greater body mass.

Aged↗
PubMed1992

Effect of sucrose diet on expression of apolipoprotein genes A-I, C-III and A-IV in rat liver.

A sucrose-rich diet stimulates hepatic lipogenesis and induces net production of very low density lipoproteins in the liver. To study changes of hepatic apolipoprotein gene expression in response to such a diet, we measured the mRNA abundance of apolipoproteins A-I, C-III and A-IV in livers of rats fed a sucrose-rich diet or a control diet for 3 weeks. In livers of sucrose-fed rats, the abundance of cellular and nuclear apo A-IV mRNA increased to 185% +/- 21% and 142% +/- 22% of control values (P less than 0.01), respectively. In sucrose-fed rats, the transcriptional activity of the apo A-IV gene, measured in a cell-free transcription system using isolated liver nuclei, increased to 144% +/- 23% of control (P less than 0.05). In contrast, this diet neither affected the abundance of cellular and nuclear apo A-I and apo C-III mRNA nor the transcriptional activity of these genes in liver. These results are consistent with specialization of the regulatory elements of the genes coding for apolipoproteins A-I, C-III and A-IV. Alternatively, enhanced transcription of the apo A-IV gene may preclude increased synthesis of apo A-I and/or apo C-III mRNA due to the close linkage of the three genes in the rat genome.

Animals↗
PubMed1992

Differential regulation of hepatic apolipoprotein A-I and A-II gene expression by thyroid hormone in rat liver.

Apolipoproteins A-I and A-II (apo A-I, apo A-II) are major protein components of high density lipoproteins. Thyroid hormone has a differential effect on the expression of the apo A-I and apo A-II genes in rat liver. Apo A-I gene expression is stimulated by thyroid hormone, whereas apo A-II mRNA abundance is decreased in chronic hyperthyroidism. To determine the regulatory steps involved in this differential effect of thyroid hormone on hepatic apo A-I and apo A-II gene expression, we studied the effect of short term and chronic hyperthyroidism on apo A-I and apo A-II gene transcription rates, nuclear RNA abundance and total cellular mRNA levels. After a single receptor saturating dose of L-triiodothyronine (T3) apo A-II gene transcription was transiently increased to 164% +/- 13% of basal values (P < 0.05) without affecting nuclear apo A-II RNA abundance. Apo A-I gene transcription, however, increased to 158% +/- 8% of baseline levels (P < 0.05) and remained elevated for at least 24 h. Nuclear and total cellular apo A-I mRNA increased more than expected from the increased transcription rate suggesting nuclear RNA stabilization and/or more efficient processing of the primary transcripts. In chronic hyperthyroidism, total cellular apo A-II mRNA abundance decreased to 62% +/- 18% (P < 0.05) and apo A-II gene transcription and apo A-II nuclear RNA were moderately reduced. By contrast, apo A-I nuclear and total cellular RNA were increased several fold by post-transcriptional mechanisms, whereas apo A-I gene transcription was drastically decreased. We conclude that the apo A-I and apo A-II genes in rat liver respond differently to both acute and chronic hyperthyroidism and that their expression is regulated at transcriptional and posttranscriptional levels.

Animals↗
PubMed1992

Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state.

The status of fasting triglycerides as a risk factor for coronary artery disease (CAD) has been considered weak because in multivariate analyses, triglycerides tend to be eliminated by high density lipoprotein (HDL) cholesterol. To further evaluate the role of triglycerides in CAD, we employed postprandial lipemia as a more informative means of characterizing triglyceride metabolism. In 61 male subjects with severe CAD and 40 control subjects without CAD as verified by angiography, we measured cholesterol; triglycerides; HDL cholesterol; HDL2 cholesterol; and apolipoproteins A-I, A-II, and B in fasting plasma and triglycerides before and 2, 4, 6, and 8 hours after a standardized test meal. Both the maximal triglyceride increase and the magnitude of postprandial lipemia (area under the triglyceride curve over 8 hours after the meal) were higher in cases than in control subjects. Single postprandial triglyceride levels 6 and 8 hours after the meal were highly discriminatory (p < 0.001), and by logistic-regression analysis displayed an accuracy of 68% in predicting the presence or absence of CAD. In this respect, accuracy was higher than that of HDL2 cholesterol (64%) and equal to that of apolipoprotein B (68%), the most discriminatory fasting parameter. Multivariate logistic-regression analysis was performed to reduce the number of risk factors to those that were statistically independent. This statistical procedure selected postprandial but not fasting triglycerides into the most accurate multivariate model, which also contained the accepted risk factors HDL2 cholesterol, apolipoprotein B, and age. This model classified 82% of subjects correctly. We conclude that triglycerides are independent predictors of CAD in multivariate analyses including HDL cholesterol, provided that a challenge test of triglyceride metabolism such as postprandial lipemia is used. The study suggests that the metabolism of triglycerides is a critical determinant of cholesterol metabolic routing. The findings support the concept that the negative association between HDL cholesterol levels and CAD actually originates in part from a positive relation between CAD and plasma triglycerides, as ascertained in the postprandial state.

Adult↗
PubMed1992

Different reactivities of high density lipoprotein2 subfractions with hepatic lipase.

Human high density lipoproteins2 (HDL2) consist of particles that contain both apolipoprotein (apo) A-I and apoA-II (A-I/A-II-HDL2) and others that contain apoA-I but are devoid of apoA-II (A-I-HDL2). When postprandial lipemia is pronounced, a fraction of HDL2 is converted into HDL2-like particles. These HDL3 exhibit lower apoA-I/apoA-II ratios than the parent HDL2, suggesting preferential conversion of A-I/A-II-HDL2 into HDL3 (J. Clin. Invest. 1984. 74: 2017-2023). Triglyceride transfer from triglyceride-rich lipoproteins to HDL2 and subsequent lipolysis by hepatic lipase are thought to mediate the conversion of HDL2 into HDL3. To understand why A-I/A-II-HDL2 are preferentially converted into HDL3, we separated postprandial HDL2 into A-I-HDL2 and A-I/A-II-HDL2 species by immunoaffinity chromatography using a monoclonal antibody for apoA-II, and determined the ability of HDL2 species i) to participate in protein-mediated lipid transfer; and ii) to interact with hepatic lipase in vitro. Triglyceride transfer from/to triglyceride-rich lipoproteins was similar for the two HDL2 species. In contrast, A-I/A-II-HDL2 were twice as effective as A-I-HDL2 in liberating hepatic lipase immobilized on HDL3-Sepharose. Lipolysis of triglycerides by hepatic lipase was 60% higher in postprandial A-I/A-II-HDL2 than in postprandial A-I-HDL2. Hydrolysis of phosphatidylcholine by hepatic lipase was threefold higher in A-II-containing HDL2 when compared with HDL2 devoid of apoA-II. The different lipolytic rates in HDL2 subspecies correlated with the size reduction of substrate lipoproteins. Reconstitution of postprandial A-I-HDL2 with apoA-II enhanced the rate of lipolysis by hepatic lipase to that observed in A-I/A-II-HDL2. We conclude that it is the interaction with hepatic lipase rather than the rate of triglyceride transfer that results in the preferred conversion of postprandial A-II-containing HDL2 into HDL3, and that apoA-II exerts a crucial role in this process.

Apolipoprotein A-I↗
PubMed1991

Regulation of PGI2 activity by serum proteins: serum albumin but not high density lipoprotein is the PGI2 binding and stabilizing protein in human blood.

Although previous studies have shown that serum albumin binds PGI2 and protects it from rapid degradation, it remains debatable whether it is physiologically important due to its low binding affinity for PGI2. We were intrigued by the observations of Yui et al. (J. Clin. Invest. 82 (1988) 803-807) which suggested that apo A-I of the high density lipoprotein (HDL) is the "serum PGI2 stabilizing factor". To clarify this, we carried out experiments to determine the binding kinetics and parameters of HDL and albumin purified from normal pooled human serum. Despite the use of multiple binding assays, we could not detect any binding activity in HDL2, HDL3 or nascent HDL preparations, nor could we demonstrate any PGI2 protecting activity by these molecules. By contrast, purified albumin exhibited essentially identical binding parameters as the native serum from which the albumin was purified. The binding activity of various albumin preparations was not due to the contamination of apo A-I. Computer simulation analysis also failed to provide evidence to support the notion that HDL bound and prolonged PGI2 activity. To determine whether physiological concentrations of albumin influence PGI2 binding to platelet receptors, we measured PGI2 binding to platelet membrane in the absence and presence of albumin. Albumin at 40 mg/ml increased the KD of PGI2 binding to the receptors by 2-3 fold. These findings indicate that albumin plays a major role in protecting PGI2 activity and regulating its availability for platelet PGI2 receptors.

Apolipoprotein A-I↗
PubMed1991

Lipoprotein(a) and apolipoprotein changes after cardiac transplantation.

Although lipoprotein changes after cardiac transplantation have been documented, the effects of transplantation and subsequent immunosuppressive therapy (particularly the combination of prednisone, azathioprine and cyclosporine) on apolipoprotein levels and lipoprotein(a) have not been reported. Fasting cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein A-1 and B-100 and lipoprotein(a) were evaluated in 69 consecutive patients during the waiting period before cardiac transplantation. There were 28 deaths before donor organ identification and 41 patients received a cardiac allograft. The lipoprotein levels of transplant recipients were again assayed 3 months postoperatively. Mean (+/- SEM) values increased for total plasma cholesterol (from 180 +/- 8 to 228 +/- 8 mg/dl, p less than or equal to 0.001), triglycerides (from 126 +/- 11 to 207 +/- 14 mg/dl; p less than or equal to 0.001), HDL cholesterol (from 39 +/- 2 to 49 +/- 3 mg/dl; p less than or equal to 0.002) and LDL cholesterol (from 119 +/- 7 to 138 +/- 7 mg/dl; p less than 0.02). Apolipoprotein A-1 and B-100 also increased, but lipoprotein(a) decreased from 11.7 +/- 1.7 to 6.8 +/- 1.1 mg/dl; p less than or equal to 0.0001) after transplantation. Although total cholesterol, triglycerides, LDL cholesterol, apolipoprotein A-1 and B-100 increased dramatically after cardiac transplantation, so did HDL cholesterol, thereby keeping the LDL/HDL cholesterol ratio constant. The surprising decrease in lipoprotein(a) after cardiac transplantation suggests that metabolism of lipoprotein(a) is independent of LDL cholesterol and that immunosuppressive drugs either decrease the synthesis or increase catabolism of lipoprotein(a).

Apolipoproteins↗
PubMed1991

Role of apolipoprotein E and B gene variation in determining response of lipid, lipoprotein, and apolipoprotein levels to increased dietary cholesterol.

A large segment of the population is modifying its dietary cholesterol intake to achieve a healthier life-style. However, all individuals do not respond equally. We have investigated the effects that that two physiologically important polymorphisms in the apolipoprotein (apo) E and B genes have on the responses of plasma lipid, lipoprotein, and apolipoprotein levels to a high-cholesterol diet. Over a 6-wk period, individuals were prescribed two diets, one consisting of 300 mg dietary cholesterol/d for 3 wk and one consisting of 1,700 mg dietary cholesterol/d for 3 wk. Total cholesterol, low-density-lipoprotein cholesterol (LDL-C), and apo B levels were significantly increased on the high-cholesterol diet. Average total cholesterol (numbers in parentheses are SDs) went from 167.6 (23.4) mg/dl on the low-cholesterol diet to 190.8 (36.2) mg/dl on the high-cholesterol diet; LDL-C went from 99.9 (24.8) mg/dl to 119.2 (33.4) mg/dl, and apo B went from 74.9 (24.5) mg/dl to 86.8 (29.5) mg/dl. In 71 individuals, the frequencies of the apo epsilon 2, epsilon 3, and epsilon 4 alleles were .09, .84, and .07, respectively. The frequency of the longer, apo B signal peptide allele (5'beta SP27) was .68. Apo epsilon 2/3 individuals had significantly lower LDL-C levels than did epsilon 3/3 homozygotes, on both the low-cholesterol diet (LDL-C lower by 21 mg/dl) and the high-cholesterol diet (LDL-C lower by 27 mg/dl). Average triglyceride levels were significantly different among apo B signal peptide genotypes, with the 5'beta SP27/37 homozygotes having the lowest levels (70 mg/dl). When individuals were switched from the low-cholesterol diet to the high-cholesterol diet, in no case were the average responses in lipid levels significantly different among apo E or B genotypes. Therefore, these gene loci do not have a major effect on the response of lipid levels to increased dietary cholesterol.

Adult↗
PubMed1991

Influence of short term dietary cholesterol and fat on human plasma Lp[a] and LDL levels.

The relationship between plasma levels of Lp[a] and LDL was examined using dietary regimens. In 81 normolipidemic male outpatients, dietary cholesterol was increased by consuming six eggs per day from a mean (SD) level of 311 (162) to 1430 (198) mg per day. Mean (SD) LDL-cholesterol levels increased from 102 (26) mg/dl to 120 (33) mg/dl (P less than 0.001), while mean (SD) Lp[a] levels were 5.5 (6.1) mg/dl on the basal diet and 5.6 (6.4) mg/dl on the cholesterol-rich diet. No significant correlation was observed between increases in either LDL-cholesterol or apolipoprotein B to Lp[a], nor was there any relationship between individual baseline levels of Lp[a] and dietary-induced changes of Lp[a]. Fourteen of the 81 participants were reexamined under strict nutritional control. Four diets with 40% of calories as fat, but differing in the type of fat and the amount of cholesterol, were administered sequentially to all subjects. As expected, mean (SD) LDL-cholesterol and apolipoprotein B levels were highest on the saturated fat, high cholesterol diet (112 (32) mg/dl and 79 (22) mg/dl) and lowest on the polyunsaturated fat, low cholesterol diet (77 (27) mg/dl and 53 (18) mg/dl). In contrast, mean Lp[a] levels did not significantly change among the four diets (range 4.2-4.9 mg/dl). No correlation of Lp[a] responses with changes in plasma lipids, apolipoproteins, or lipoproteins was observed on any diet. These data suggest that determinants of plasma Lp[a] levels are distinctly different from the determinants of plasma LDL levels in normolipidemic males.

Adult↗
PubMed1990

ARIC hemostasis study--II. Organizational plan and feasibility study.

In our previous paper, we reported the development of a blood collection and processing system (BCPS) suitable for the ARIC multicenter hemostasis study. As an additional step of preparation for the ARIC study, we incorporated this BCPS into an organizational plan to increase efficiency and minimize errors. We initially designed organizational trays for blood collection tubes and aliquot tubes and developed a coordinated step-by-step plan for the orderly processing of blood samples. Once the plan was considered workable, we carried out a pilot study to test the feasibility of this integrated organizational plan. Included in the pilot study were 95 healthy subjects randomly selected from 4 ARIC field centers, whose age and gender were comparable to those projected for the ARIC population. We determined the time lapse of filling the first tube as an index of blood flow. The overall mean time-lapse was 23 s (S.D. = 5). There was no significant difference among the field centers. We also determined the entire time lapse required for completing the sample processing. The total processing time was always less than 60 min. By performing the processing of samples in pairs, all the samples from two subjects could be completely processed in 70 min. This greatly increased the efficiency of field center operation. We evaluated the potential in vitro hemostasis activation by measuring plasma beta-thromboglobulin and platelet factor 4 levels. The geometric means of both proteins were comparable to our previously reported results. Fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin III, protein C and activated partial thromboplastin time were analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1990

Development of cholesterol homeostatic memory in the rat is influenced by maternal diets.

The hypothesis that dietary factors in early life modify the extent of adaptive responses in adult life was tested in rats. During the gestational and lactational periods, pregnant rats were fed either a high-fat (HF) or low-fat (LF) diet (corn oil, 15% or 2%, wt/wt) until 30 days postpartum. The offspring were maintained on standard chow for an additional 100 days and fed a HF diet for 1, 3, 7, or 21 days. Upon challenge for 3 days, rats born to dams fed the HF diet showed a more rapid hypercholesterolemic response when compared with rats born to dams fed a LF diet (mean +/- S.D., 151 +/- 14 mg/dL v 122 +/- 6 mg/dL; P less than .001). Higher levels of cholesterol were associated with elevated levels of apolipoprotein (apo) B (24.0 +/- 4 mg/dL v 15.8 +/- 3 mg/dL; P less than .05) and apo E (31.0 +/- 4 mg/dL v 24.7 +/- 3 mg/dL; P less than .05). Further comparison of the hypercholesterolemic response between the two groups of animals showed increases in cholesterol in all major lipoprotein classes, cholesterol enrichment at the expense of triglyceride (TG) in very-low-density lipoprotein (VLDL), and elevation of apo E-containing high-density lipoprotein (HDL). Examination at longer time periods of HF challenge showed that apo E levels of the HF-exposed animals remained elevated compared with similarly challenged rats born to dams fed the LF diet (35 +/- 3.8 mg/dL v 26 +/- 2.7 mg/dL; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of alcohol dose on plasma lipoprotein subfractions and lipolytic enzyme activity in active and inactive men.

Controversy as to which lipoprotein subfraction of high-density lipoprotein (HDL) increases during alcohol consumption prompted the current study of the effects of two alcohol doses over varying time intervals on plasma lipoproteins and lipolytic enzymes. Measurements were made in 49 healthy men before and after three weeks of abstinence from alcohol and after consumption of one or three 12-ounce cans of beer per day. We found that HDL (10%), HDL2 (14%), and HDL3 (9%) cholesterol, and apolipoprotein A-I (7%) decreased with abstinence from alcohol and then increased with its consumption. These increases were not significant until after 3 weeks of daily alcohol intake, but they were significant in both the one-can and three-cans of beer per day groups. In the 23 inactive subjects HDL and HDL2 cholesterol decreased with abstinence but did not increase significantly with alcohol intake. Lipolytic enzymes were not changed by alcohol manipulation, but the level of lipoprotein lipase was higher and that of hepatic lipase was lower at each measurement point in the 26 habitually active versus the 23 inactive subjects. Adjustment for weight or skinfold thickness did not affect lipoprotein changes over time within groups but did eliminate many of the differences between activity groups. Alcohol consumption seems to be related to possibly beneficial influences on plasma HDL and HDL2 cholesterol, and may thus impact the risk of heart disease.

Adult↗
PubMed1990

Role of thyroid hormones in apolipoprotein A-I gene expression in rat liver.

To study the regulation of hepatic apo A-I gene expression, we measured synthesis and abundance of cellular apo A-I mRNA and its nuclear precursors in livers of hypothyroid and hyperthyroid rats. In hypothyroid animals, both synthesis and abundance of apo A-I mRNA was reduced to half of control values. After injection of a receptor-saturating dose of triiodothyronine into euthyroid rats, apo A-I gene transcription increased at 20 min, reached a maximum of 179% of control (P less than 0.01) at 3.5 h, and remained elevated for up to 48 h. The abundance of nuclear and total cellular apo A-I mRNA increased at 1 and 2 h, respectively, and exceeded the levels expected from enhanced transcription more than two fold at 24 h after hormone injection. Upon chronic administration of thyroid hormones, levels of nuclear and cytoplasmic apo A-I mRNA remained elevated but transcription of the apo A-I gene fell to 42% of control (P less than 0.01). Thus, thyroid hormones rapidly stimulate apo A-I gene transcription. Posttranscriptional events leading to increased stability of nuclear apo A-I RNA precursors become the principal mechanism for enhanced gene expression in chronic hyperthyroidism and may cause feedback inhibition of apo A-I gene transcription. Our results furthermore imply that the majority of hepatic nuclear apo A-I RNA precursors are degraded in euthyroid animals.

Albumins↗
PubMed1990

Variation in concentration of lipids, lipoprotein lipids, and apolipoproteins A-I and B in plasma from healthy women.

The components of total variation--biological, inter- and intra-individual, and analytical--of plasma lipids, lipoprotein lipids, and apolipoproteins A-I and B have been determined in a population of 44 healthy women, ages 18-35 years. Blood was sampled three separate times at three-month intervals, with no restrictions on diet or physical activity during these periods. The greatest inter-individual variances were observed for high-density lipoprotein (HDL)-cholesterol, HDL2-cholesterol, and total plasma cholesterol. Triglycerides had the highest intra-individual variance (CV 22%). The percentage of inter- and intra-individual variances of apolipoprotein A-I concentrations were more reflective of total HDL- and HDL2-cholesterol content than of HDL3-cholesterol. Concentrations of calculated low-density-lipoprotein cholesterol showed a greater inter-individual variation (18.6%) than did apolipoprotein B (10.7%). The laboratory CVs for these analytes were similar to other reported values. From these data, we computed the expected variation for subjects in our study for single and repeated measurements. Such considerations can influence decision-making in the clinical setting or in designing epidemiological studies.

Adolescent↗
PubMed1990

Polymorphic forms of human apolipoprotein[a]: inheritance and relationship of their molecular weights to plasma levels of lipoprotein[a].

The plasma concentration of human lipoprotein[a], Lp[a], is highly correlated with coronary artery disease. The protein moiety of Lp[a], apoLp[a], consists of two apoproteins, apo[a] and apoB-100, linked by one or more disulfide bonds(s). Apo[a], the protein unique to Lp[a], exists in polymorphic forms that exhibit different apparent molecular weights (Mr). Polyacrylamide gel electrophoresis in sodium dodecyl sulfate followed by immunoblotting was used to separate and visualize these different forms and to determine the polymorphic pattern of apo[a] in the plasma samples of 692 individuals. A total of 11 different polymorph bands ranging in Mr from 419 kD to 838 kD could be resolved, but only 1 or 2 bands were present per individual. The polymorphic band pattern for an individual was assigned to 1 of the 66 different phenotype designations representing the total number of possible single- and double-band combinations of the 11 detectable bands. All 11 of the possible single-band phenotypes but only 32 of the 55 possible double-band phenotypes were represented. There were 412 plasma samples (59.5%) that contained a single band, 274 (39.6%) contained two bands, and only 6 (0.9%) had no detectable apo[a] band. A highly significant inverse correlation was found between the Mr of the band(s) present and the plasma apoLp[a] concentration (r = -0.461; rho = 0.0001). The correlation was better between apoLp[a] and single-band (r = -0.495; rho = 0.0001) than double-band (r = -0.382; rho = 0.0001) phenotypes. Of the 274 individuals exhibiting double-band phenotypes, the lower Mr band was more intense in 141 (51.4%), the two bands were equally intense in 85 (31.0%), while the higher Mr band was more intense in 48 (17.5%). Based upon the hypothesis that apo[a] polymorphism is controlled by different alleles at a single locus, the frequency of the 11 alleles determined from the observe phenotypes (low Mr----high Mr) was: band 1) 419 kD, 0.00875; band 2) 489 kD, 0.00510; band 3) 536 kD, 0.0555; band 4) 553 kD, 0.0758; band 5) 613 kD, 0.135; band 6) 680 kD, 0.0824; band 7) 705 kD, 0.104; band 8) 742 kD, 0.151; band 9) 760 kD, 0.246; band 10) 796 kD, 0.128; band 11) 838 kD, 0.00802. The observed distribution of phenotypes in the population was compared by chi-square analysis to that predicted on the basis of simple Mendelian inheritance, and the hypothesis was rejected (chi 2 = 921.7; rho less than 0.001). Significantly, the singleband phenotypes are over-represented in the population compared to that predicted.(ABSTRACT TRUNCATED AT 400 WORDS)

Apolipoproteins A↗