Variation In Serum Cholesterol Research Articles

Interindividual variation in serum cholesterol is associated with regional white matter tissue integrity in older adults

Prior research has demonstrated links among vascular health and the occurrence of stroke, mild cognitive decline, and dementia in older adults. However, little is known about whether normal variation in vascular indicators may be related to changes in neural tissue integrity. Even less is known about how the brain is affected by cholesterol levels in the normal to moderate risk range, leading up to overt disease pathology. This study examined associations between serum lipid levels and DTI indicators of white matter (WM) structural integrity in a sample of 125 generally healthy older adults aged 43-87 years. Whole-brain voxelwise analysis, controlling for age and gender, revealed low density lipoprotein levels (LDL) as the most robust correlate of regional WM structural integrity of the measured lipids. Higher LDL was associated with decreased WM integrity in right frontal and temporal regions, the superior longitudinal fasciculus and internal/external capsules. Increasing LDL was associated with increased radial and axial diffusivity; however, more widespread statistical effects were found for radial diffusivity. These findings suggest that normal interindividual variation in lipid levels is associated with compromised regional WM integrity, even in individuals below clinical thresholds for hyperlipidemia. Given the prevalence of cholesterol-associated sequelae in older adults, and mounting evidence suggesting a vascular role in the etiology of dementia, the current data suggest that understanding the relationship between cholesterol and brain tissue microstructure may have important clinical implications for early detection of vascular-related cognitive disorders and optimal regulation of serum lipids to maintain neural health in older adults.

Genetic, epigenetic, and gene-by-diet interaction effects underlie variation in serum lipids in a LG/J×SM/J murine model

Variation in serum cholesterol, free-fatty acids, and triglycerides is associated with cardiovascular disease (CVD) risk factors. There is great interest in characterizing the underlying genetic architecture of these risk factors, because they vary greatly within and among human populations and between the sexes. We present results of a genome-wide scan for quantitative trait loci (QTL) affecting serum cholesterol, free-fatty acids, and triglycerides in an F(16) advanced intercross line of LG/J and SM/J (Wustl:LG,SM-G16). Half of the population was fed a high-fat diet and half was fed a relatively low-fat diet. Context-dependent genetic (additive and dominance) and epigenetic (imprinting) effects were characterized by partitioning animals into sex, diet, and sex-by-diet cohorts. Here we examine genetic, environmental, and genetic-by-environmental interactions of QTL overlapping previously identified loci associated with CVD risk factors, and we add to the serum lipid QTL landscape by identifying new loci.

Within-person variation in serum lipids: implications for clinical trials.

Little is known about the degree to which behavioural, biological, and genetic traits contribute to within-person variation in serum cholesterol. Materials and Methods The authors studied within-person variation in serum total and high density lipoprotein (HDL) cholesterol in 458 participants of 27 dietary intervention studies in Wageningen, The Netherlands, from 1976 to 1995. For a median of 4 days between blood draws, the geometric mean of the within-person standard deviation was 0.13 mmol/l ( approximately 5 mg/dl, coefficient of variation = 3.0%) for total cholesterol and 0.04 mmol/l ( approximately 1.5 mg/dl, coefficient of variation = 3.0%) for HDL cholesterol. In mixed-model linear regressions using within-person variance as the dependent variable and including lipid concentration and covariates listed below, within-person variance of both total cholesterol and HDL cholesterol was higher for greater number of days between blood draws and for self-selected diet rather than investigator-controlled diet. Within-person variance of total cholesterol only was higher for non-standardized versus standardized phlebotomy protocol and for female sex. The authors found evidence that the APOA4 -347 (12/22 genotype) and MTP -493 (11 genotype) polymorphisms may increase the within-person variation in total cholesterol. Under certain study design (self-selected diet, use of non-standardized phlebotomy protocol) or participant characteristics (female, certain polymorphisms) within-person lipid variance is increased and required sample size will be greater. These findings may have important implications for the time and cost of such interventions.

Age-associated changes in integral cholesterol and cholesterol sulfate concentrations in human scalp hair and finger nail clippings

In contrast to surface lipids originating from the sebaceous glands, membrane-forming integral lipids occur in keratinized tissues of skin, and skin appendages like fingernail plates or scalp hair. After removal of lipids of sebaceous origin by exhaustive solvent extraction, lyophilizing and hydrolyzing fingernail plate and scalp hair samples, fractions of integral cholesterol (CH) and cholesterol sulfate (CS) were quantified using gas chromatography. We studied these bound lipids and the serum lipids of 70 healthy subjects, aged 20.1 to 92.0 years. We observed higher amounts of CS in hair clippings of men than of women (775+/-241 vs 662+/-239 nmol/g hair, respectively). The highest amounts of CS were found in men with serum LDL-CH > 4.14 mmol/L; this subgroup also showed the highest CH values in fingernail clippings (2293+/-621 nmol/g nail). However, analysis of integral lipids of hair and fingernail plate clippings had little significance in detecting hypercholesterolemia in normal persons. An increase in integral CH levels in fingernail clippings with donor age was noted, independently of variations in serum CH or LDL-CH. This correlation proved to be significant in men (R=0.43), but not in women (R=0.38). In contrast, in women but not in men we found donor age correlated with internal CH of hair samples (R=0.43) and with CS of nail plates (R=-0.59), independently of serum CH or LDL-CH variations. This age-dependent decrease in CS levels might explain the previously observed higher incidence of brittle nails in women. Obviously, the metabolism of internal lipids CH and CS in fingernail and scalp hair differs between genders, and shows age-associated changes.

Circannual variations in blood cholesterol levels.

The seasonality of blood cholesterol is still not well established. Some have described a seasonal pattern with highest levels during autumn and lowest in summer, whereas others have reported no change. A number of studies showed circannual variations with maximum levels in winter and minimum in summer. The aim of this study was to examine the circannual variation of cholesterol in a large cohort in Israel. In the Israeli CORDIS study, employees of 21 factories were screened for cardiovascular disease risk factors during 1985-7. As part of the information gathered, serum cholesterol and blood counts were available for 3,726 men and 1,514 women. Serum cholesterol levels fit a circannual rhythm assessed by the cosinor analysis. Highest levels of serum cholesterol were found in spring and lowest in summer. We conclude that there is a circannual change of serum cholesterol, which could be partially associated with changes in environmental temperature. The circannual variation in serum cholesterol was considerable and should be taken into account when carrying out clinical evaluation of patients.

Studies on the mechanism of induction of hypercholesterolemia in rabbits by high dietary levels of amino acids

Increasing the proportion of an amino acid mixture corresponding to casein in a low-fat, cholesterol-free, semipurified diet fed to rabbits causes a progressive increase in serum total and low density lipoprotein cholesterol, and the effect appears to be due primarily to the essential amino acids in the mixture. Our recent studies have also shown that the variations in serum cholesterol in response to different levels of the amino acid mixture are not associated with any changes in fecal excretion of cholesterol or bile acids. Further attempts to understand the mechanism of action of dietary amino acids on serum cholesterol levels have shown the following: (1) no correlation with levels of plasma amino acids, either in the fasting or postprandial state: (2) no correlation with serum levels of thyroid hormones: (3) no relationship to activity of hepatic or intestinal microsomal hydroxymethylglutaryl coenzyme A reductase: (4) no corresponding effects on the activities of cholesterol esterifying enzymes of intestinal mucosa: and (5) no correlation with the degree of esterification of cholesterol in very low or low density lipoproteins. Further studies are required to identify the specific amino acids responsible for the hypercholesterolemic effects and to determine the mechanisms involved.

Apolipoprotein E polymorphism determined by restriction enzyme analysis of DNA amplified by polymerase chain reaction: convenient alternative to phenotyping by isoelectric focusing

Three common alleles determine six apolipoprotein E (apo E) phenotypes that are associated with variations in serum cholesterol in the population. This genetic variation results from single nucleotide alterations at two DNA loci encoding the amino acid residues 112 and 158 of apo E. We compared results of apo E phenotyping carried out by isoelectric focusing with those of apo E genotyping accomplished by direct DNA analysis. In the latter, the target DNA was amplified by the polymerase chain reaction (PCR) and subsequently analyzed by digestion with the restriction enzyme Hha I, followed by polyacrylamide gel electrophoresis of the cleavage products. With one exception, these two techniques yielded similar results from all 40 samples tested. In addition, a rare variant form of apo E (phenotype E1) was analyzed separately and incorrectly diagnosed as E2 by the Hha I digestion method; the anticipated mutation in the codon 127 was, however, confirmed by demonstration of a new Taq I restriction site in this variant gene. These data confirm that the common isoforms of apo E usually arise from genetic variation of the codons 112 and 158 and demonstrate the feasibility of the PCR technique in apo E genotyping.

Serum cholesterol as a predictor of performance and carcass quality in growing pigs

Cholesterol plays an important role in the transport of lipid throughout the body. Moreover, reports have linked the turnover of cholesterol with obesity (eg Nestel, Schreibman and Ahrens, 1973). Recent studies have demonstrated wide variations in serum cholesterol in response to hypercholesterogenic diets in growing pigs (Shutler and Low, 1988). These variations in response appear to have a genetic basis and may be due to variations in turnover rates. The aim of the present study was to determine whether the measurement of serum cholesterol in growing pigs, either in their normal state or after being given a dietary cholesterol challenge, could be used in the prediction of performance or carcass quality.

A comparison of direct measures of glycaemia and glycated blood proteins in insulin-dependent diabetes mellitus

We have studied associations between various direct measures of glycaemia and glycated blood proteins in 113 subjects with insulin-dependent diabetes mellitus (IDDM), and examined whether or not the 'fructosamine' assay results were affected by differing patient serum concentrations of lipids, albumin or C peptide. Serum fructosamine correlated less closely with HbA1 (r = 0.44) than did HbA1 with glycated serum albumin (GSA) (r = 0.68). Serum fructosamine and GSA also were poorly correlated (r = 0.48). Although fructosamine, HbA1 and GSA correlated to a similar degree with fasting blood glucose (r range 0.34 to 0.37), GSA was most closely related to mean blood glucose (r = 0.39 vs. 0.30-0.35) and the M value (a marker of diurnal glycaemic instability) (r = 0.42 vs. 0.33-0.35). The serum concentration of fructosamine was not significantly affected by a variation in serum cholesterol, but tended to be lower in subjects with moderate hypertriglyceridaemia (p = 0.05). The fructosamine assay may be altered by moderately lipaemic serum but is not affected by serum albumin concentration in normoalbuminaemic patients with IDDM. Our study indicates, however, that GSA is a more reliable marker of short-term glycaemic control in IDDM than fructosamine.

Overview: Seasonal variations in cholesterol

There is a common belief that strong evidence supports significant seasonal variations in serum cholesterol. An examination of 19 studies from 1965 to 1979 suggests that the evidence for seasonal variation is not compelling and that some of the earlier studies suffered from a serious methodological error of analysis: comparing means with extreme values. This practice is demonstrated to result in significant findings which are mathematical artifacts rather than meaningful characteristics of distributions.

Apparent influence of marker genotypes on variation in serum cholesterol in monozygotic twins.

Ninety-seven monozygotic (MZ) twin pairs were grouped by marker system genotypes, and mean intrapair differences in serum total cholesterol level were compared between groups. Significant differences were found when the MNs and the Kidd blood group systems were considered. The results appear to suggest a restrictive effect of certain normal marker genes on environmentally caused variation in serum cholesterol level.

Analysis of genetic and environmental sources of variation in serum cholesterol in Tecumseh, Michigan-VI. A search for genotype by environment interaction

We have examined 12 unlinked polymorphic genetic marker systems and found 6 which each identified small but statistically significant differences in normal serum cholesterol levels which did not change significantly with age. The effects associated with 4 of the 6-ABO haptoglobin, Gm and secretor—were consistent in males and females and combined additively to define effects which were also homogeneous over age. There was a marker phenotype by age interaction effect on cholesterol variance in females but not in males. This study supports the hypothesis that a number of polymorphic genes, each with a small additive effect on cholesterol level, play an important role in determining cholesterol variability.

Analysis of genetic and environmental sources of variation in serum cholesterol in Tecumseh, Michigan. V. Variance components estimated from pedigrees

The human geneticist who wishes to estimate the genetic and environmental components of a quantitative trait has the choice of several sampling designs. Sets of monozygous and dizygous twins, parents and their offspring, and full siblings are often the most convenient samples but invariably yield estimators of genetic variance which are biased by shared environmental factors. More recently, fixed combinations of related and unrelated individuals have been proposed as sampling strategies to improve the separation of genetic and shared environmental correlations between relatives. These fixed designs take the form of family sets (Schull et al. 1970; Chakraborty et al. 1977) or sets of monozygous twins, their spouses and offspring (Nance & Corey, 1976). Unfortunately, human data cannot easily be collected according to a fixed design. A convenient sample usually consists of families which vary in the genetic relatedness of their members. Most human studies have utilized regression coefficients and interclass correlations estimated from pairs of individuals or intraclass correlations from subsets of individuals selected from a random sample of families. These statistics are generally contrasted to estimate the fractions of phenotypic variance due to genetic and environmental factors. The strategies available for combining these estimators do not adequately account for the double counting of individuals and alleles which may occur. For example, the full sib correlations and the parent-offspring correlations are usually estimated from individuals drawn from the same array of nuclear families. Elston (1975) has shown that the correlations between these correlation estimates may not be trivial. Despite the obvious implication, the precise effect of using correlated estimates on inferences about heritability estimates is not clear at this time. In order to minimize the inflation of type I1 error it is not uncommon to discard a large portion of the data. For example, in the Tecumseh Community Health Study, from the 6366 individuals typed for 12 blood markers, less than 100 genetically independent family sets, consisting of an index, a sib and a cousin could be constructed (Orr, personal communication). If the assumption of independence of family sets was rigorously met, only 5 yo of the available data could be utilized and the effect of the nonindependent index-sib and index-cousin correlations would still be unresolved. More importantly, samples of pairs or sets of relatives are usually not randomly sampled and therefore may not represent the same phenotypic variability of a quantitative trait that is determined by t,he frequency distribution of genotypes and environments among and within pedigrees which define the population. Alternatively, we may use the procedure of maximum likelihood estimation (MLE) to combine all of the information available in a sample of randomly selected pedigrees to obtain

Analysis of genetic and environmental sources of variation in serum cholesterol in Tecumseh, Michigan: II. The role of education, occupation, and income.

Analysis of genetic and environmental sources of variation in serum cholesterol in Tecumseh, Michigan: II. The role of education, occupation, and income.

Seasonal variation of non-embolic cerebral infarction

IT IS well accepted today that the prevalence of diseases caused by microorganisms is altered by climatic fluctuations. The increased incidence of pulmonary infection [l] in the winter and of poliomyelitis and gastro-intestinal infections in the summer are the best examples of this and probably reflect a combination of variations in (1) the host’s susceptibilities; (2) bacterial or viral virulence; and (3) vector availability. Stroke should not have a seasonal variation unless the major causative factors underlying its precipitation, including for instance atherosclerosis and circulatory dynamics, are modified by climate and season. Such factors as eating and drinking habits vary with the temperature; summer dehydration may alter circulatory dynamics and lead to cerebral infarction. There are suggestions of a seasonal variation in cholesterol levels in a stable population of men aged 46-62. Cholesterol levels were found to be highest from November to March and lowest during the summer months, May through August [2, 31. In a similar study involving both sexes, males and females showed seasonal variations of cholesterol levels in opposite directions [4]. Protein bound iodine levels have been found to vary seasonally, the lowest values found during June, July and August with high values in September, October, February and March [4]. The gap between these suggestions of seasonal variation in serum cholesterol and PBI and the occurrence of stroke is too wide for any meaningful connection. Some evidence for a seasonal variation in atherosclerotic disease is found in studies of coronary heart disease. Death from cardiovascular disease in some parts of the United States has a peak during December to April with a low point in August and September [6, 71. The reduction of death rates during the summer months has been confirmed in studies in areas with a marked seasonal climatic variation but not in areas which are continuously warm [S]. In Australia cardiovascular deaths are higher during their winter months, June through September, and lowest during their summer months, January through April [9]. In the field of cerebrovascular disease Takakashi in Japan found that cerebral hemorrhage had a low incidence in the summer months, June to September, and a high incidence in the winter months [IO].

Study of serum lipid levels in twins.

The influence of genetic and environmental factors on the variation in serum cholesterol, triglyceride, phospholipid, and β-lipoprotein levels was investigated by means of a twin study of 108 like-sex twin pairs. The results suggest that genetic influences are weak, and that environmental influences are established before twins separate to live apart.

Seasonal variation in serum lipids, and incidence and mortality of ischaemic heart disease

Analysis of serum lipid estimations performed in the routine laboratory of the Atheroma Research Unit during 1965 and 1966 showed a highly significant variation in serum cholesterol. The highest levels occurred in the spring and the lowest in the autumn. Serum triglyceride levels did not follow a definite seasonal pattern. There was no direct correlation between seasonal variation in serum cholesterol and seasonal variation in either the incidence or mortality of ischaemic heart disease.

SERUM CHOLESTEROL LEVELS OF INBRED RATS.

Changes in serum cholesterol levels with age have been studied in male and female rats of three inbred strains (BN, DA, and Lewis) and one random-bred strain (Wistar). The mean serum cholesterol levels at each age differed among strains. Serum cholesterol levels (mg/100 ml) for male rats at 30, 60, and 90 days were: BN-65, 46, and 47; DA-105, 85, and 101; Lewis-79, 76, and 57; and Wistar-64, 63, and 73. For female rats the values were: BN-56, 45, and 47; DA-86, 74, and 91; Lewis-77, 83, and 67; and Wistar-59, 71, and 83. The variation of serum cholesterol with age was different between strains, but similar for males and females within each strain. There was no correlation between body weight and serum cholesterol. Liver cholesterol levels (mg/100 g) determined at 90 days were, for the males, BN-187, DA-233, Lewis-247, and Wistar-300, and for the females, BN-188, DA-244, Lewis-216, and Wistar-249. No correlation with body weight or serum cholesterol was observed.

EFFECT OF INDOOR HOUSING CONDITIONS ON SERUM CHOLESTEROL LEVELS OF WHITE CARNEAU PIGEONS.

SummaryOld White Carneau pigeons maintained under regulated light (9 hr fluorescent light, 15 hr darkness), temperature (76 ± 2°C), and humidity (about 40%) conditions and in groups of 6 in cages that do not permit flying for a period of over 18 months do not have the seasonal cyclic variations in serum cholesterol possessed by pigeons that have free access to flying areas and are exposed to yearly weather conditions.

Multicentre trial in the united kingdom and ireland of a mixture of ethyl chlorophenoxyisobutyrate and androsterone (atromid): A preliminary report*

Summary The results of a multicentre trial of Atromid in 601 patients have been presented. (1) The response to treatment does not differ markedly with the severity of the hypercholesterolaemia, the absolute reduction varying from 35 % for those with high initial levels to 26 % for those with low initial levels. (2) Female patients had higher initial cholesterol levels, but their response was otherwise similar to the males. (3) A marked seasonal variation in serum cholesterol of untreated patients was observed and it was apparent that the seasonal effect was not completely masked by treatment. (4) The response of 42 diabetics and 37 patients with xanthomatosis did not differ from that of the remainder. (5) Hypertensives responded in the same way as normotensive subjects. (6) An apparently paradoxical relationship between the cholesterol response and dose expressed in terms of body weight was observed. A possible explanation for this is suggested and no significance is attached to the observation. (7) Patients treated concurrently with unsaturated fats appeared to respond rather better during the early months of the trial, but this difference disappeared after the 3rd month. (8) Twenty-one deaths occurred during the trial, which is considered to have been too short for any conclusions to be drawn about the effect of Atromid on survival. (9) Concurrent use of anticoagulants resulted in haemorrhage in 26 patients and in death in 2. The great majority of these incidents occurred before the potentiating effect of Atromid was appreciated. (10) Side-effects, most commonly in the form of mild gastro-intestinal upset, were reported in 119 cases, most frequently in the first month of treatment. (11) No change in serum uric acid was detected on the pre-treatment levels. (12) No change in serum bilirubin was observed. (13) SGPT levels appeared to fall between the 2nd and 4th month but this fall is not statistically significant. (14) SGOT levels were examined in detail in 2 trials. A significant increase in SGOT was reported in both trials. The SGOT levels in smaller groups of patients were within the mean levels for these 2 trials. No simple explanation could be found for the variable results in different studies.