Prevalence of familial hyper- and hypolipoproteinemias: the Princeton School District Family Study.
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Biomedical subjects
Publications and source records attributed to P M Laskarzewski.
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A general linear model is described here for cultural and biological inheritance of lipids and lipoproteins. This model involves 10 parameters to be estimated from a total of 17 correlations, leaving ample degrees of freedom to test the goodness of fit. The model fits very well to each of the five lipid and lipoprotein variables analyzed here from a Lipid Research Clinic family data set. Both genetic and cultural inheritance are significant for each trait with the single exception that triglyceride levels fail to support genetic inheritance. Under the most parsimonious hypothesis, the genetic heritability (h2) ranges from .194 +/- .092 for triglyceride to .624 +/- .093 for low-density lipoprotein-cholesterol. Cultural heritability ranges from .070 +/- .030 for total cholesterol to .149 +/- .034 for triglyceride.
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The aim of this study was to assess parent-child interactions of coronary heart disease risk factors (total cholesterol, high and low density lipoprotein cholesterols, systolic and diastolic blood pressures, and relative ponderosity) in parents and their pediatric-aged children in the Princeton School study. The study population included 430 parent-child pairs from 301 families. Forty-seven of these 301 families were "nuclear" (both parents and at least one child) and included 118 parent-child pairs. Univariate analyses of covariance were used to assess parent-child risk factor interactions and interrelationships. Interdependent coronary heart disease risk factor relationships were extensively shared by parents with their children. Knowledge of parental risk factor levels and their relationships and interactions with children's risk factor levels should be useful in identifying children at presumptively increased long-term risk as adults, and should illuminate metabolic relationships between parents and children for coronary heart disease risk factors.
The effects of sucrose polyester (SPE) (a nonabsorbable mixture of hex-a, hepta,- and octa-fatty acid esters of sucrose with physical properties similar to those of common dietary fats) on fecal bile acid excretion and composition were assessed in 24 healthy, nonobese, normolipemic male volunteers, in a 40-day, inpatient, metabolic balance study. Isocaloric diets provided either 800, 300, or less than 50 mg of cholesterol/day (P/S ratios respectively 0.4, 1.0, and 1.5). After diet-only perids of 10 days (for the 800 and 300 mg cholesterol regimens), and 21 days (for the 50 mg diet), the diets were continued for 30 days, with addition of SPE to diets over three successive treatment periods of 10 days each, with 8, 16, and 35 g of liquid SPE/day, or 15, 30, and 50 g SPE/day in a SPE-hydrogenated palm oil mix. On both the liquid SPE and SPE-hydrogenated palm oil mix, there were no significant changes in fecal bile acid excretion as a function of dietary SPE, at any level of cholesterol intake, P > 0.1. In most subjects SPE changed fecal bile acid composition; lithocholic acid was decreased, and in most instances this was accompanied by the appearance and increase in chenodeoxycholic acid. In one subject, both deoxycholic and 3 beta, 12 alpha-dihydroxycholanic acid were reduced, with an accompanying increase in cholic acid. The hypocholesterolemic effect of SPE appears to be mediated through its reduction of intestinal absorption of cholesterol, not through effects on bile acid excretion.
The purpose of this report was to assess intrafamilial associations of lipids between related and unrelated household members seen in the course of a population-based survey of lipids in schoolchildren and their parents. Fasting plasma total cholesterol and triglyceride levels were measured in 6,857 and 3,079 adults. Age effects were removed for each sex-race group using a third-degree polynomial regression of lipid on age; the residuals were then used as observations in the analyses. For both cholesterol and triglyceride, significant positive correlations existed between father and son, father and daughter, mother and son, and mother and daughter. For both cholesterol and triglyceride, although the mother-child correlations were stronger than those for father-child, they were not significantly different. There were no significant correlations between step, foster, or adoptive parents and children. For cholesterol in sibships of size two, intrasibship correlations for fully related siblings were 0.333, for half-sibs 0.164, and for unrelated sibs, 0.085. Consistently closer intrafamilial cholesterol and triglyceride associations between related than unrelated family members, and the strong parental effects on cholesterol and triglyceride indicate, in aggregate, that a considerable proportion of the variation of cholesterol and triglyceride can be explained by genetic factors.
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The role of major genes in the expression of serum uric acid (UA) levels was investigated in data collected from five clinics of the Lipid Research Clinics (LRC) family study. Over 2,000 randomly ascertained individuals were analyzed. The UA distributions were homogeneous among the five LRC clinics and between the parental and offspring generations. This result suggested that the data could be pooled across clinics, thereby increasing the statistical power associated with larger sample sizes for testing various null hypotheses. Additionally, a mixture of three normal distributions best characterized the combined-clinics data. Segregation patterns were examined in the untransformed data, as well as in a more conservative (and biologically meaningful) log transformation. Prior to log transformation, both major and multifactorial effects were detected. The major effect was not transmissible, i.e., was not compatible with Mendelian transmission, and accounted for 39% of the variance in UA levels. However, after the log transform was applied to the data and the segregation analysis was repeated, support for the major effect disappeared altogether and only the multifactorial component remained, accounting for 50% of the variation in offspring and 19% in patients.
We used the Princeton School Family Study hypercholesterolemic recall group to assess whether, and to what degree, the identification of hypercholesterolemic subjects could be improved through the phenomenon of familial lipid and lipoprotein aggregation. A second aim was to assess whether within-family lipid and lipoprotein correlations outlasted the period of shared family environment. Approximately twice as many (as expected) siblings and offspring of hypercholesterolemic probands had plasma total and low density lipoprotein cholesterol levels greater than the 90th and 75th percentiles respectively, emphasizing how identification of hypercholesterolemic subjects can be facilitated by use of the phenomenon of familial aggregation of plasma total and low density lipoprotein cholesterol. After exclusion of the hypercholesterolemic probands from calculations of within-family correlations, and use of natural log transformations for the probands' first-degree relatives' lipids as required, most father/pediatric offspring and mother/pediatric offspring correlations for lipids and lipoprotein cholesterols were significant, while most parent/adult offspring correlations were not significant. All pediatric sibling correlations for lipids and lipoprotein cholesterols were significant; most adult sibling correlations were not significant. The loss of significance and consistency in sibling and parent/offspring lipid and lipoprotein correlations in adults who no longer shared a common household environment points to environmental influences on total, high, and low density lipoprotein cholesterol in kindreds with a hypercholesterolemic proband.
Our specific aim in this study was to assess the family resemblance for lipids and lipoproteins in blacks randomly selected from the Princeton School District's Family Study cohort, and compare the family resemblance of lipids and lipoproteins between the blacks and whites from the same cohort. There were 160 white and 59 black nuclear families ascertained through randomly selected family study probands. Familial correlations were estimated by the method of maximum likelihood. Father-child and sib-sib correlations were of larger magnitude in whites than blacks for each lipid and lipoprotein, with the exception of high density lipoprotein cholesterol, where the correlations in blacks were higher than in whites. Estimates of genetic heritability were larger in whites than in blacks for each lipid and lipoprotein, with the exception of high density lipoprotein cholesterol. Whereas environment has a substantial effect on high density lipoprotein cholesterol levels in both blacks and whites, there may be a greater genetic effect accounting for higher levels of high density lipoprotein cholesterol in blacks. This is highlighted in our current study by the consistent observation in blacks of increased measures of within-family resemblance for high density lipoprotein cholesterol alone, of all lipids and lipoproteins.