Familial hypoalphalipoproteinemia.
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Cholesterol, HDL↗
Biomedical subjects
P M Laskarzewski
Publications and source records attributed to P M Laskarzewski.
Frequency and clustering of nonlipid coronary risk factors in dyslipoproteinemia. The Lipid Research Clinics Program Prevalence Study.
In a defined population of 4349 men and 3398 women, we evaluated the frequency and clustering of five nonlipid coronary heart disease risk factors--obesity, hypertension, sedentary lifestyle, cigarette smoking, and alcohol consumption--in nine categorical lipoprotein phenotypes--normal, types I or V, IIA, IIB, III, IV, hypoHDL (high-density lipoprotein), hypoLDL (low-density lipoprotein), and hyperHDL. This analysis indicated that compared with the normal phenotype, nonlipid coronary risk factors tend to be more frequent and thus cluster in individuals with "high risk" phenotypes, and occur somewhat less frequently in those with "low risk" phenotypes. Thus, identification of a high-risk phenotype suggests the presence of nonlipid risk factors as well, and the clinician should be alert to this possibility. A multivariable analysis of the independent associations of each of the risk factors with the lipid and lipoprotein components that define the phenotypes suggested that several behavioral risk factors may directly affect lipid and lipoprotein levels. This observation raises the possibility that certain intervention strategies, such as weight loss, smoking cessation, and regular exercise, may favorably influence dyslipoproteinemia.
Adult↗
Progeny's lipid and lipoprotein levels by parental mortality. The Lipid Research Clinics Program Prevalence Study.
Using data from Lipid Research Clinics study participants at visit 2 (3972 and 2346 adult men and women), we examined the hypothesis that parental mortality from cardiovascular disease (CVD) or cancer before age 60 predicts their adult progeny's lipid and lipoprotein levels. Weighted regression analysis was used to control for the potential effect of progeny's other CVD risk factors (age, systolic blood pressure, Quetelet index, cigarette smoking, and alcohol consumption), and to assess for the effect of progeny's parental cause-specific mortality status on progeny's lipids and lipoproteins. Nearly all of the statistically significant parent-progeny predictions were for sons. Paternal death from CVD before age 60 years was associated with significantly higher plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels in sons and (at marginal significance) in daughters, when compared with those in reference progeny with paternal survival over age 60 or over age 75. Maternal death from CVD before 60 was associated with lower levels of high-density lipoprotein cholesterol (HDL-C) in sons. Paternal and maternal death from cancer before age 60 years were associated with higher triglyceride levels in adult sons than in sons whose parents had lived beyond ages 60 and 75. Paternal all-cause mortality before age 60 was associated with higher cholesterol and triglycerides in sons; maternal all-cause mortality before age 60 was associated with depression of HDL-C in sons. Familial aggregation of lipids and lipoproteins may account, in part, for familial aggregation of CVD. Knowledge of family history facilitates identification of progeny at higher risk for CVD by virtue of elevated cholesterol or LDL-C, or reduced HDL-C.
Adult↗
A major gene for primary hypoalphalipoproteinemia.
Sixteen kindreds were ascertained through probands clinically determined to have primary hypoalphalipoproteinemia, characterized by bottom decile high-density lipoprotein cholesterol (HDL-c), but otherwise normolipidemic. Age- and sex-adjusted, standardized HDL-c levels on 64 individuals in 14 nuclear families in which the proband was a parent were analyzed using the unified mixed model of segregation analysis as implemented in the computer program POINTER. The analysis proceeded by using the likelihood of offspring conditional on the parental phenotypes (conditional likelihood), which appears to overcome the limitation of possible heterogeneity in the selection criteria and provides an appropriate correction for the ascertainment. In these families, the multifactorial contribution to the phenotype appears to be small and significant only in the offspring generation. Although it was not possible to resolve the dominance pattern at the major locus since none of a recessive, additive, or dominant hypothesis could be firmly rejected, these families provided clear evidence for a major gene. Genetic heterogeneity is still a possibility, even within "primary" hypoalphalipoproteinemia.
Cholesterol, HDL↗
Tracking of high- and low-density-lipoprotein cholesterol from childhood to young adulthood in a single large kindred with familial hypercholesterolemia.
Tracking of high- and low-density-lipoprotein cholesterol (HDLC, LDLC) from childhood to young adulthood was assessed in 77 children and in 53 adults from a single large pedigree with familial hypercholesterolemia who were respectively less than or equal to 19 and greater than or equal to 20 years old when first studied in 1973, with reassessment in 1984. No children and only five of the adults had received LDLC lowering therapy from 1973 to 1984. The rank correlations between the 1973 and 1984 measurements for LDLC were 0.73, 0.74, and 0.87; and for HDLC were 0.55, 0.73, and 0.65 (P less than 0.0001 for all correlations), respectively for relatives who were less than or equal to 12, 13 to 19, and greater than or equal to 20 years old in 1973. The 1973:1984 LDLC and HDLC correlations, categorized by relationships to the proband, were as follows: (1) unrelated, LDLC = 0.16, HDLC = 0.56;* (2) first-degree relatives, LDLC = 0.90, HDLC = 0.30; (3) second-degree relatives, LDLC = 0.79, HDLC = 0.39; and (4) other relatives, LDLC = 0.62, HDLC = 0.64. All nine of the probands' first-degree relatives who were above the age-sex specific LDLC 95th percentile in 1973 were also greater than the 95th percentile for LDLC in 1984. Similarly, seven of eight second-degree relatives with LDLC greater than the 95th percentile in 1973 were greater than the 95th percentile in 1984, as were ten of 15 other relatives. LDLC levels in childhood in this extended kindred were highly predictive of adult values.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
A genetic study of hypoalphalipoproteinemia.
Complex segregation analysis under the unified mixed model of inheritance (major gene and multifactorial) is performed on families ascertained through 23 probands with hypoalphalipoproteinemia (depressed HDL-cholesterol, denoted HDL-c). Evidence for segregation of a recessive major gene for depressed HDL-c with frequency q = 0.116, in addition to multifactorial transmission (H = 0.572), is found in these families. Reanalysis of a subset of families with severely depressed HDL-c confirms the conclusions based on the original analysis, except that different definitions of "affection" give rise to different estimates of gene frequency. Our finding of a recessive mode of inheritance differs from previous claims for a dominant gene because previous analyses did not use a mixed model for segregation analysis of hypoalphalipoproteinemia. When the significant multifactorial background is neglected, we also find evidence for the invalid claim of a dominant gene. This demonstrates the necessity of using mixed models for determining the mode of inheritance of a given phenotype.
Cholesterol, HDL↗
The Cincinnati Lipid Research Clinic Family Study: analysis of commingling and family resemblance for fasting blood glucose.
Our specific aim in this study was to investigate commingling and family resemblance for fasting blood glucose in 160 randomly selected white families from the Princeton School District Lipid Research Clinics Family Study. Adjustment of fasting blood glucose for the influence of age, sex, and the use of oral contraceptives and construction of indices were performed simultaneously using multiple regression methods. Path analysis was carried out, constructing an environmental index based on special diet usage, hematocrit, and obesity, which was also adjusted for the influences of age and sex. Commingling analysis and segregation analysis using the mixed model were also performed. Nearly 16% of the variance of fasting blood glucose was accounted for by age and sex. Obesity itself, which constituted the index, explained an additional 4% of the variance of fasting blood glucose. Significant genetic heritability for fasting blood glucose was documented by both path analysis and segregation analysis. In aggregate, we conclude that though there was a major familial vector accounting for within-family aggregation of blood glucose, it was probably generated by a multifactorial component as compared to a major locus. Under the most parsimonious model, path analysis estimated the genetic and cultural heritabilities as h2 = .39 +/- .08 and c2 = .06 +/- .03., respectively.
Age Factors↗
High-density lipoprotein cholesterol in blacks and whites: potential ramifications for coronary heart disease.
Black male and female juveniles and adult black males have higher levels of high-density lipoprotein (HDL) cholesterol than do whites, differences that potentially "protect" them against augmented coronary heart disease morbidity and mortality, given an excess of certain coronary heart disease risk factors among blacks, particularly hypertension. The loss of the "protective" HDL cholesterol difference in adult black females appears most likely to be due to their pandemic obesity. Inasmuch as blacks smoke more, are more likely to have diabetes, and are more often treated with antihypertensives, these factors would tend to reduce black-white differences in HDL cholesterol. Black-white differences in alcohol intake and habitual and leisure-time physical activity would not be likely, in the aggregate, to affect black-white differences in HDL cholesterol. It thus seems likely that, whereas environment has a substantial effect on HDL cholesterol for blacks and whites, there may be a "genetic" vector accounting for higher levels of HDL cholesterol in blacks.
Adolescent↗
Severe depression of high-density lipoprotein cholesterol levels in weight lifters and body builders by self-administered exogenous testosterone and anabolic-androgenic steroids.
The effects of nonphysician prescribed, self-obtained, self-administered exogenous anabolic-androgenic steroids and testosterone on plasma total, high- and low-density lipoprotein cholesterol (HDLC, LDLC), and triglycerides were evaluated in 14 adult white men, 11 body builders and 3 power weight lifters. Lipids and lipoprotein cholesterols were quantified during active physical conditioning, both on (for at least 1 month, mean +/- SD 1.8 months) and off (for at least 4 months, 7.3 +/- 2.7 months) self-administered exogenous androgenic steroids. The subjects took 50 to 100 mg methandrostenolone daily plus weekly injections of testosterone 100 to 200 mg and nandrolone decanoate 100 to 200 mg per week. Mean (SD) HDLC on exogenous androgenic steroids, 29 +/- 8 mg/dL, was severely depressed, and was less than 50% of the consistently elevated mean HDLC when exogenous steroids were not used (61 +/- 14 mg/dL, P less than .01 for paired differences). During anabolic steroid use, HDLC was less than or equal to the age- race- and sex-specific 10th percentile in 11 of the 14 men, whereas while off anabolic steroids, HDLC was greater than or equal to the 90th percentile in 7 of the 13 men, and in the top quartile for 3 of the remaining 6 men. Mean LDLC was higher on androgenic steroids (150 +/- 44) than off (125 +/- 38 mg/dL), P less than .05 for paired differences. The ratio of LDLC/HDLC during exogenous steroid use (6.0 +/- 3.7) was nearly triple the ratio obtained when steroids were not taken (2.2 +/- 1.0), P less than .01 for paired differences.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cincinnati Lipid Research Clinic.
A major limitation of the Collaborative Lipid Research Clinic's Family Study and hence, the Princeton School District's Family Study, was the insufficient data gathering relative to environmental influences, particularly nutrient intake, alcohol intake, smoking, habitual physical activity, recent weight gain and loss, etc. (Laskarzewski 1983c). In addition, inadequacies of quantitation of family history further represented major problem areas (Laskarzewski 1982c). Nevertheless, the Princeton School District Family Study had major utility in documenting within-family aggregation of CHD risk factors in children and their young adult parents in an economically variegated, biracial cohort.
Adolescent↗
Parent-offspring and sibling body mass index associations during and after sharing of common household environments: the Princeton School District Family Study.
Using the Princeton School Family Study cohort, our specific aim was to determine whether, and to what degree, parent-offspring and sibling associations for measures of body habitus outlast the period of shared common household environment in a single well characterized community. Familial associations of measures in body habitus were assessed in two and three generation kindreds, in parents and their pediatric offspring (less than 20-yr-old), parents and their adult offspring (less than or equal to 20-yr-old), and in pediatric and adult siblings. The cohort included 177 randomly recalled probands and 202 probands from a hyperlipidemic recall group (top decile plasma cholesterol and/or triglyceride). In randomly recalled whites, significant associations of body mass indices in parents and pediatric offspring and in pediatric siblings, and the absence of significant correlations in parents and adult offspring and in adult siblings, emphasize the potency of common household environmental effects relative to within-family similarities for shared body habitus. In whites from the hyperlipidemic recall group, only the mother-pediatric and adult offspring correlations for body mass indices were significant. We speculate that mothers and their offspring from kindreds selected by hyperlipidemic probands are more likely than fathers and their offspring to share eating habits and relative ponderosity, with these communal behaviors outlasting the period of common household environment. Alternatively, and speculatively, in the hyperlipidemic recall group, determinants for ponderosity may be shared more by mothers and their offspring than by fathers and their offspring. Particularly in the random recall group, within-family associations of body mass indices primarily reflect shared common household environments, and probably secondarily, the outcome of genes held in common.
Adolescent↗
Familial hyper- and hypouricemias in random and hyperlipidemic recall cohorts: the Princeton School District Family Study.
Using the Princeton School Family Study, our specific aim was to estimate the prevalence of familial hyper- and hypouricemia, to estimate the proportion of probands' first-degree relatives who were similarly affected, and to evaluate the contribution of diseases, drugs, and alcohol intake (if any) to uric acid levels. We studied 379 probands and a total of 1928 subjects, 125 and 52 black probands from a randomly recalled group, 147 white and 55 black probands from a hyperlipidemic recall (top decile cholesterol and/or triglyceride) group. Familial hyper- and hypouricemias were arbitrarily identified in those kindreds having at least two first-degree relatives in the same decile as the proband, top or bottom respectively, for serum uric acid. No probands had symptomatic gout. Diseases, drugs, and alcohol intake were not consistently associated with aggregations of high and/or low uric acid levels in families, and had little relationship to uric acid levels in individuals. Of the 177 randomly recalled probands, and of the 55 black probands in hyperlipidemic recall familial hyperuricemia, with concurrent primary hyperlipoproteinemia and hypertension. Familial hypouricemia was present in 1 of 125 white and in 1 of 52 randomly recalled black kindreds, and in 3 of 147 white and 3 of 55 hyperlipidemic recall black kindreds. While familial clustering of hyperuricemia was limited, clustering of hypouricemia was much more marked. Seventy-four and 84% respectively of first-degree relatives of hypouricemic white and black probands had uric acid less than the 50th percentile. In randomly recalled probands and their first-degree relatives there were significant inverse partial correlations between uric acid and high density lipoprotein cholesterol. Inverse associations of uric acid with high density lipoprotein cholesterol and the concurrence of hyperlipoproteinemia and hypertension in hyperuricemic families points to the importance of lipoprotein and blood pressure screening in families with asymptomatic hyperuricemia. The potential ramifications of within-family clustering of hypouricemia need to be further assessed in populations, particularly in regards to uric acid nephrolithiasis.
Adolescent↗
High and low density lipoprotein cholesterols in adolescent boys: relationships with endogenous testosterone, estradiol, and Quetelet index.
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Adolescent↗
Longitudinal relationships among endogenous testosterone, estradiol, and Quetelet index with high and low density lipoprotein cholesterols in adolescent boys.
In a 1-year longitudinal study of 19 adolescent boys, our major aim was to assess whether, and to what degree, testosterone, estradiol, Quetelet index, and their interactions related to concentrations of high and low density lipoprotein cholesterol (HDLC, LDLC). During the 1-year followup, mean HDLC and estradiol levels fell and triglycerides, LDLC, Quetelet index, and testosterone levels rose. For large decreases in estradiol, increases in testosterone were associated with decreases in HDLC. These decreases in HDLC were moderated by small decreases in Quetelet index. For boys with small decreases in estradiol, as the changes in testosterone increased, the change in HDLC varied from an increase to a decrease, except in those boys who also had a small decrease in Quetelet index, for whom the change in HDLC was positive. The greatest increases in LDLC were observed in boys having the largest increase in Quetelet index and a small decrease in estradiol; however, as the decrease in estradiol became large, the positive association of Quetelet with LDLC was moderated or nullified. For boys having large decreases in estradiol, the LDLC/HDLC ratio changed from small increments to substantial decrements as testosterone increased. As the decreases in estradiol became smaller, increases in the change of testosterone moderated the decreases in the LDLC/HDLC ratio, and large increases in Quetelet index tended to diminish this moderation. As the change in testosterone increased, the change in triglyceride increased, unless the decrease in estradiol was small. The overall pattern of change of HDLC and LDLC during sexual maturation in boys can be associated with changes in testosterone, estradiol, and Quetelet index.
Adipose Tissue↗
Familial obesity and leanness.
Using the Princeton School District Family Study cohort, our specific aim was to estimate the prevalence of suspected familial ponderosity and leanness, to provide empirical risk estimates for the proportion of probands' first-degree relatives who were similarly affected, and to estimate the contributions of diseases, drugs and caloric intake to relative obesity and leanness. We studied 379 probands, 125 whites and 52 blacks from a random recall group, 147 whites and 55 blacks from a hyperlipidemic recall group. Suspected familial obesity and leanness were arbitrarily identified in those kindreds with at least two first-degree relatives in the same Quetelet index decile as the proband, top or bottom respectively. Suspected familial obesity was observed in 2.4 percent and 6 percent respectively of random and hyperlipidemic recall group whites. Suspected familial leanness was identified in 2.4 percent and 1.4 percent of random and hyperlipidemic recall whites and in 3.8 percent of randomly recalled blacks. Approximately twice as many as expected white first-degree relatives of top Quetelet index decile probands themselves had top decile Quetelet indices; approximately three times as many as expected first-degree relatives of bottom decile Quetelet index probands themselves had bottom decile Quetelet indices. Nineteen percent and 31 percent of top decile Quetelet index white probands from random and hyperlipidemic recall groups came from families where at least two other first-degree relatives were similarly obese; 18 percent and 20 percent of white random and hyperlipidemic recall group probands with bottom decile Quetelet indices had suspected familial leanness. Nearly all subjects with familial obesity or leanness had no overt metabolic or pharmacological explanations for their body habitus. Within-family clustering of hypertension was common in kindreds with suspected familial obesity and was absent in kindreds with suspected familial leanness. Marked within-family clustering of both obesity and leanness is useful diagnostically; therapeutic intervention to reduce obesity, to be most effective, should be family-wide in the many kindreds which share familial obesity.
Adolescent↗
Heterogeneity between populations for multifactorial inheritance of plasma lipids.
A general linear model was described for multifactorial inheritance of the two plasma lipids, total cholesterol (CH), and triglyceride (TG). Analyses of two separate studies, the Honolulu Heart Study (HHS) and the Cincinnati Lipid Research Clinic (LRC), indicated some heterogeneity. Whereas the sibling environmental effect (b) was the only source of heterogeneity between the two studies for TG, the correlation between marital environments (u) may also be considered as a source of heterogeneity for CH. Under parsimonious hypothesis, intergenerational differences in heritabilities were not found to be significant for either trait (y1 = y2 = z1 = z2 = 1). Maternal effects were significant for CH but not for TG. Correlations between marital environments (u1 and u2) were not significant for TG, and may be considered nonsignificant for CH also under parsimonious hypotheses. In any case, the genetic (h2) and cultural (c2) heritabilities cannot be considered to be heterogeneous between the two studies. Based on pooled data, parsimonious hypothesis yields: h2 = .594 +/- .041 and c2 = .035 +/- .008 for CH, and h2 = .259 +/- .034 and c2 = .108 +/- .014 for TG.
Aged↗
The Clinical Lipid Research Clinic Family Study: familial determinants of plasma uric acid.
Commingling analysis of plasma uric acid levels in a random sample of 160 nuclear families supports the hypothesis that there is a mixture of three distributions. Assuming one, two, and three components in the underlying distribution, we obtained the corresponding p-values (for power transformation) as 0.059, 1.040, and 1.643, respectively. Path analysis with p = 0.059, 1.040, and 1.643 respectively. Path analysis with p = 0.059 gives genetic (h2) and cultural (c2) heritabilities as 0.256 and 0.199, without much support for intergenerational differences, assortative mating, or maternal effects. Complex segregation analysis with p = 0.059 supports multifactorial inheritance, consistent with the findings of Gulbrandsen et al. (1979) and Morton (1979) in other populations. This study also fails to support a major locus hypothesis, contrary to earlier reports.
Adolescent↗
A simulation study of parameter estimation in the one and two compartment models.
Few attempts have been made to examine the statistical problems that the user of compartmental models must face. Some properties of the estimators of parameters for one and two compartmental models based on nonlinear estimation were studied through simulation. Of particular interest were the effect of the experimental design and the effect of different error structures on the empirical sampling distribution for the estimators. For the one compartment model it was found that nonlinear estimation yielded essentially unbiased estimators that were normally distributed unless the random error for the model was large. In the two compartment model simulations, bias appeared in the estimators to the extent that bimodal sampling distributions of the estimators were observed as the random error for the model was increased.
Humans↗