Biomedical subjects

E J Schaefer

Publications and source records attributed to E J Schaefer.

At least 37 records · Page 2Linked to original sources

PubMed2001

Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study.

Apolipoprotein (apo) CIII participates in the regulation of the metabolism of triglyceride-rich lipoproteins and it is a major component of chylomicrons and VLDL. The APOC3 gene is on chromosome 11q23 and is highly polymorphic. The less common allele (S2) of the SstI polymorphism on the 3' untranslated region of the APOC3 gene has been previously associated with increased triglycerides, total cholesterol (TC), and apoCIII levels and cardiovascular risk on several, but not all, studies. The aim of this study was to examine the association of this polymorphism with plasma lipid levels, lipoprotein subfractions and coronary heart disease (CHD) risk in a population-based study: The Framingham Offspring Study. The frequency of the S2 allele was 0.086, consistent with previous reports in Caucasian populations. In men, the S2 allele was associated with lower concentrations of high-density lipoprotein cholesterol (HDL-C; P<0.04) and HDL2-C (P<0.02) and a significant increase in apoCIII non-HDL (P<0.05). TG levels were higher in men carriers of the S2 allele, but this association did not reach statistical significance (P=0.30). Conversely, in women, the S2 allele was associated with increased TC (P<0.03), low-density lipoprotein cholesterol (LDL-C; P<0.03), and ApoB levels (P<0.04). Lipoproteins subfractions were also examined using nuclear magnetic resonance (NMR) spectroscopy. S2 male carriers had significantly lower concentrations of large LDL and a significant reduction in LDL particle size (P<0.04). In women, there was a significant increase in intermediate LDL particles (P<0.05) with no significant effect on lipoprotein diameters. We also examined the associations between the S2 allele and biochemical markers of glucose metabolism. In men, the S2 allele was associated with elevated fasting insulin concentrations (P<0.04), whereas no significant associations were observed in women. Despite the described associations with lipid and glucose metabolism related risk factors, we did not find any significant increase in CHD risk associated with the S2 allele in this population.

Alleles↗

PubMed2001

Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner.

The response to therapy with hypolipidemic agents shows considerable individual variation. These differences may be due to the interaction of environmental and genetic factors that affect drug bioavailability, receptor function or ligand structure. Our objective was to assess the effect of apolipoprotein (apo) E genotype and gender on lipid-lowering response to the HMG CoA reductase inhibitor, atorvastatin. Genotyping was carried out on DNA from 328 male and female subjects who participated in a multicentric, double-blind clinical trial, and received 10 mg/day of atorvastatin. Our data demonstrate no significant gender differences for LDL cholesterol levels at baseline. Moreover, mean LDL-C lowering was similar in men (-36.2%, range -2.7 to -57.8%) and in women (-38.1%, range -9.5 to -58.5%) as compared to baseline. However, men carrying the epsilon2 allele had a significantly higher mean LDL-C response (-44%) than epsilon3 homozygotes (-37%) and epsilon4 carriers (-34%); P=0.01 for apoE group by treatment interaction. No such gene/treatment interactions were noted in women, with those carrying the epsilon2 allele showing a similar mean response (-34%) as epsilon3 homozygotes (-39%) and epsilon4 carriers (-34%). Mean plasma triglyceride lowering with atorvastatin was 17%. A significant apoE group by treatment interaction (P=0.010) was also observed in men, with epsilon2 carriers being more responsive (-27%) than epsilon3/3 (-13%) and epsilon4 (-22%). This interaction was not observed in women. In summary, atorvastatin treatment had similar effects on plasma lipid levels in both men and women; however, the apoE gene locus was a significant predictor of LDL-C and TG responses to atorvastatin therapy in men, but not in women.

Anticholesteremic Agents↗

PubMed2001

Association of the A/T54 polymorphism in the intestinal fatty acid binding protein with variations in plasma lipids in the Framingham Offspring Study.

We investigated the potential role of the genetic variation at the intestinal fatty acid binding protein gene (FABP2) in influencing lipid levels in a representative sample of the Framingham Offspring Study participants (n=1930). In men, the T54 allele was associated with significantly higher LDL-cholesterol (3.47+/-0.83 vs. 3.36+/-0.83 mmol/l; P<0.047), and ApoB (1.04+/-0.23 vs. 1.01+/-0.24 g/l; P<0.020) after adjustment for familial relationship, age, BMI, smoking, alcohol intake and the use of beta-blockers compared with the A54 allele. This relationship with ApoB continued to be significant after adjustment for APOE genotype (P<0.034). In women, the T54 allele was associated with significantly higher total-cholesterol (5.32+/-1.01 vs. 5.17+/-0.98 mmol/l; P<0.049) and LDL-cholesterol (3.31+/-0.93 vs. 3.18+/-0.85 mmol/l; P<0.023) after adjustment for covariates and menopausal status, estrogen therapy and APOE genotype. In men, the T54 allele was associated with significantly higher levels of small VLDL and lower levels of large HDL. Moreover, there was no significant relationship between FABP2 alleles and lipoprotein diameter or the prevalence of coronary heart disease in both genders. Our data are consistent with the T54 IFABP increasing the flux of lipids through the enterocyte leading to an increase in chylomicron secretion.

Age Distribution↗

PubMed2001

Cholesterol and apolipoprotein B metabolism in Tangier disease.

Tangier disease (TD), caused by mutations in the gene encoding ATP-binding cassette 1 (ABCA1), is a rare genetic disorder in which homozygotes have a marked deficiency of high density lipoproteins (HDL), as well as concentrations of low density lipoproteins (LDL) that are typically 40% of normal. Although it is well known that the reduced levels of HDL in TD are due to hypercatabolism, the mechanism responsible for the low LDL levels has not been defined. Recently, it has been reported that intestinal cholesterol absorption is altered in ABCA1 deficient mice, suggesting that aberrant cholesterol metabolism may contribute to the LDL reductions in TD. In order to explore this possibility, as well as to define the role that ABCA1 plays in the metabolism of apolipoprotein (apoB)-containing lipoproteins, we determined the kinetics of apoB-100 within lipoproteins, and cholesterol absorption, biosynthesis, and turnover, in a compound heterozygote for TD. The levels of HDL cholesterol, LDL cholesterol and LDL apoB-100 in this subject were 7, 27 and 69% of normal, respectively, the latter of which was due to a two-fold increase in LDL catabolism (0.54 vs. 0.26+/-0.07 poolsday(-1)) relative to controls (n=11). NMR analysis of plasma lipoproteins revealed that 91% of the LDL cholesterol in the TD subject was contained within small, dense LDL, as compared with only 20% for controls (n=70). Cholesterol absorption was 97% of the value for controls (n=15) in the TD subject, at 45%, with cholesterol synthesis and turnover increased modestly by 17 and 25%, respectively. Our data are consistent with the concept that the reductions of LDL observed in TD are due to enhanced catabolism, secondary to changes in LDL composition and size, with neither cholesterol absorption nor metabolism significantly influenced by mutations in ABCA1.

ATP Binding Cassette Transporter 1↗

PubMed2001

Alcohol drinking determines the effect of the APOE locus on LDL-cholesterol concentrations in men: the Framingham Offspring Study.

BACKGROUND: The effect of alcohol drinking on LDL-cholesterol concentrations is unclear. The reported variability may be due to interactions between genetic factors and alcohol intake. OBJECTIVE: The purpose of the study was to examine whether variation at the apolipoprotein E gene (APOE) locus modulates the association between alcohol drinking and LDL cholesterol. DESIGN: We used a cross-sectional design in a healthy population-based sample of 1014 men and 1133 women from the Framingham Offspring Study. RESULTS: In male nondrinkers (n = 197), LDL cholesterol was not significantly different across APOE allele groups [APOE*E2 (E2), APOE*E3 (E3), and APOE*E4 (E4)]. However, in male drinkers (n = 817), differences were observed (P: < 0.001); those with the E2 allele had the lowest concentrations. LDL cholesterol in men with the E2 allele was significantly lower in drinkers than in nondrinkers but was significantly higher in drinkers than in nondrinkers in men with the E4 allele. This APOE-alcohol interaction remained significant (P < 0.001) after age, body mass index, smoking status, and fat and energy intakes were controlled for. In women, the expected effect of APOE alleles on LDL cholesterol occurred in both drinkers (n = 791; P < 0.001) and nondrinkers (n = 342; P < 0.001). Multiple linear regression models showed a negative association (P < 0.05) between alcohol and LDL cholesterol in men with the E2 allele but a positive association in men with the E4 allele. No significant associations were observed in men or women with the E3 allele. CONCLUSION: In men, the effects of alcohol intake on LDL cholesterol are modulated in part by variability at the APOE locus.

Adult↗

PubMed2001

Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet.

BACKGROUND: Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet. OBJECTIVE: This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia. DESIGN: Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group). RESULTS: Subjects in the low- and high-sterol groups who consumed > or = 80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control). CONCLUSION: A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia.

Adult↗

PubMed2001

Association of sex, adiposity, and diet with HDL subclasses in middle-aged Chinese.

BACKGROUND: There is limited information regarding the associations of lifestyle factors and sex with HDL subclasses containing apolipoprotein (apo) A-I (Lp A-I) and both apo A-I and apo A-II (Lp A-I:A-II). OBJECTIVE: We sought to examine the relations between 2 major HDL subclasses and sex, menopausal status, nutrient intakes, and adiposity. DESIGN: We conducted interviews and measured blood variables in 409 government employees aged 40-59 y in Taiwan. RESULTS: Women (n = 203) had significantly higher concentrations of HDL cholesterol, Lp A-I, and Lp A-I:A-II than did men (n = 206). Postmenopausal women (n = 72) had higher concentrations of HDL cholesterol, Lp A-I, and Lp A-I:A-II than did premenopausal women (n = 131). Body mass index and waist-to-hip ratio were strong predictors of and exerted an independent additive effect on Lp A-I concentrations in both men and women. However, body adiposity was associated with Lp A-I:A-II concentrations only in men. Waist-to-hip ratio was an independent determinant of Lp A-I but not of Lp A-I:A-II in men and postmenopausal women after adjustment for age, body mass index, smoking, and diet. Although there were relatively weak associations between dietary factors and both HDL subclasses (r = 0.01-0.26) in men and women according to bivariate analyses, multiple regression models showed that total fat, saturated fat, and cholesterol intakes were significantly correlated with HDL cholesterol and both Lp A-I and Lp A-I:A-II in men, but not in women. CONCLUSION: Our data suggest that body adiposity and dietary fat consumption affect 2 major HDL subclasses differently depending on subject sex and menopausal status.

Adipose Tissue↗

PubMed2001

Effects of a National Cholesterol Education Program Step II Diet on apolipoprotein A-IV metabolism within triacylglycerol-rich lipoproteins and plasma.

BACKGROUND: Apolipoprotein (apo) A-IV is a major component of triacylglycerol-rich lipoprotein (TRL) apolipoproteins. OBJECTIVE: We investigated the effects of dietary saturated fat and cholesterol restriction on the metabolism of TRL and plasma apo A-IV. DESIGN: We assessed TRL and plasma apo A-IV kinetics in 16 and 4 subjects, respectively, consuming an average US (baseline) diet for 6 wk and a National Cholesterol Education Program Step II diet for 24 wk, respectively. At the end of each diet period, all subjects received a primed, constant infusion of deuterated leucine for 15 h with hourly feeding. Ratios of stable-isotope tracer to tracee were measured by using gas chromatography-mass spectrometry, and kinetic data were modeled by using SAAM II. RESULTS: Mean apo A-IV concentrations during the isotope infusion period were 6.9 +/- 2.6 mg/L in TRL and 2.2 +/- 3.2 mg/L in plasma with the baseline diet; these values were 37.7% (P < 0.001) and 19.4% (P < 0.01) lower with the Step II diet. Similar changes were observed in the fasting state between the 2 diets. The mean apo A-IV secretion rate decreased significantly from baseline by 59.6% in TRLs and by 40.2% in plasma. Significant correlations were observed between TRL apo A-IV concentrations and the secretion rate (r = 0.94, P < 0.001) and between TRL apo A-IV pool size and TRL-cholesterol concentrations (r = 0.48, P < 0.01). CONCLUSIONS: Our data indicate that the National Cholesterol Education Program Step II diet significantly decreases TRL and plasma apo A-IV concentrations compared with the average US diet and that this decrease is due to a decreased secretion rate.

Adult↗

PubMed2001

Metabolic, psychological, and health correlates of dietary restraint in healthy postmenopausal women.

BACKGROUND: Dietary restraint, a term used to describe the intentional control of food intake to prevent weight gain or promote weight loss, is commonly practiced by older adults, but little is known about its effects on physiology and metabolism. METHODS: We therefore compared a wide range of parameters between groups of healthy non-obese postmenopausal women classified psychometrically as unrestrained eaters (body mass index [BMI] 23.8 +/- 0.6 [SEM] kg/m(2), n = 28) or restrained eaters (BMI 24.5 +/- 0.5, n = 39). Measurements were made of reported micronutrient intakes, cardiopulmonary function, hematology, body temperature, skin thickness, bone mass, and immune function; in addition, self-perceived health, mood, and some dimensions of eating behavior were assessed by questionnaire. RESULTS: Macronutrient and micronutrient intakes were not significantly different between restrained and unrestrained eaters reporting energy intake to within 30% of predicted total energy expenditure. Restrained eaters had significantly lower hemoglobin (12.9 +/- 0.1 [SEM] vs 13.2 +/- 0.1 g/dl; p <.05), but values were within the normal range in both groups. In addition, restrained eaters scored significantly higher on the Eating Attitudes Test (p <.01) and drive-for-thinness (p <.001) and maturity fears (p <.05) subscores of the Eating Disorders Inventory, but values were again within the normal range. No other parameter differed significantly between groups. CONCLUSIONS: In this normal-weight population, restrained eating was not associated with detrimental effects in a wide range of physiological, metabolic, and health characteristics. Further work is needed to determine the relevance of these results to the general population.

Attitude to Health↗

PubMed2001

An oat-containing hypocaloric diet reduces systolic blood pressure and improves lipid profile beyond effects of weight loss in men and women.

Hypertension, dyslipidemia and overweight contribute substantially to cardiovascular disease risk. One of the most effective methods for improving high blood pressure and lipid profiles is loss of excess weight. Other recommendations for reducing cardiovascular risk include changes in dietary micronutrient, macronutrient and fiber intakes. To better define a diet for reduction in cardiovascular risk, 43 adults (body mass index 26.4 +/- 3.3, range 20.5-33.9 kg/m(2)) participated in an 8-wk study to determine the effects of two diets on weight, blood pressure, lipids and insulin sensitivity. For 2 wk, weight was maintained and all subjects consumed a control diet. For the next 6 wk, subjects consumed one of two hypocaloric diets (maintenance energy minus 4.2 MJ/d): the control diet (n = 21) or a diet containing oats [45 g/(4.2 MJ dietary energy. d), n = 22]. There was no significant difference between groups in changes in weight loss (control -4.0 +/- 1.1 kg, oats -3.9 +/- 1.6 kg, P = 0.8). The oats diet resulted in greater decreases in mean systolic blood pressure (oats -6 +/- 7 mm Hg, control -1 +/- 10 mm Hg, P = 0.026), whereas diastolic blood pressure change did not differ between the two groups (oats -4 +/- 6 mm Hg, control -3 +/- 5 mm Hg, P = 0.8). The oat diet resulted in significantly greater decreases in total cholesterol (oats -0.87 +/- 0.47 mmol/L, control -0.34 +/- 0.5 mmol/L, P = 0.003) and LDL cholesterol (oats -0.6 +/- 0.41 mmol/L, control -0.2 +/- 0.41mmol/L, P = 0.008). In summary, a hypocaloric diet containing oats consumed over 6 wk resulted in greater improvements in systolic blood pressure and lipid profile than did a hypocaloric diet without oats.

Adult↗

PubMed2001

Association of the Ala54-Thr polymorphism in the intestinal fatty acid-binding protein with 2-h postchallenge insulin levels in the Framingham Offspring Study.

OBJECTIVE: To investigate the association of variants of the intestinal fatty acid-binding protein gene (FABP2) with fasting and postchallenge glucose and insulin levels, HbA(1c), and prevalence of type 2 diabetes in a separate sample of men and women. RESEARCH DESIGN AND METHODS: Subjects were participants in the Framingham Offspring Study, a long-term community-based prospective observational study of risk factors for cardiovascular disease. The study sample consisted of 762 men and 922 women. RESULTS: In women, carriers of the Thr54 allele had significantly higher 2-h postchallenge insulin levels than noncarriers (104.4 +/- 73.0 vs. 93.4 +/- 61.5 microU/ml; P = 0.0139). This relationship remained significant after adjustment for familial relationship, age, BMI, triglycerides, APOE genotype, smoking, alcohol intake, the use of beta-blockers, menopausal status, and estrogen therapy. No such significant association was observed in men. In both men and women, there were no statistical associations between the FABP2 polymorphism and BMI, fasting glucose, fasting insulin, 2-h postchallenge glucose levels, HbA(1c), and prevalence of type 2 diabetes. CONCLUSIONS: These results suggest that the FABP2 Thr54 allele may have a minor contribution to the insulin resistance syndrome in a white general population.

Alanine↗

PubMed2001

Influence of photoperiod, laboratory caging and aging on plasma lipid response to an atherogenic diet among F1B hamsters.

The effects and interactions of photoperiod, animal caging, aging and diet on plasma lipid levels in male F1B hamsters were examined in the current study. Sixteen young and sixteen old animals were housed one or four per cage. Eight young animals from each housing group were placed in an animal room with either 12/12 h (PT-12) or 10/14 h (PT-10) light/dark cycle while the sixteen old animals were maintained under a PT-12 light cycle. Plasma cholesterol and triglyceride concentrations were determined in all animals after a 2-week period of acclimation on chow diet and following 4-week intervention on atherogenic diet. Baseline total cholesterol (TC) levels were 131+/-25 mg/dl and 142+/-39 mg/dl for young and old animals, respectively, while baseline triglyceride (Tg) levels were 202+/-48 mg/dl and 160+/-37 mg/dl respectively for the same animals. Following 4-weeks on an atherogenic diet, single-caged PT 12 animals had elevated but significantly lower TC levels than group-caged animals (161+/-30 mg/dl and 240 +/-58 mg/dl, respectively) while single and group housed PT10 animals had TC levels of 296+/-75 mg/dl and 351+/-124 mg/dl, respectively. Similarly, plasma Tg levels rose to 330+/-100 mg/dl and 486+/-200 mg/dl in single and group housed PT12 animals (respectively) and to 668+/-270 mg/dl and 545+/-199 mg/dl in single and group housed PT10 animals (respectively). No significant changes related to atherogenic diet were observed in plasma TC or Tg levels in the older animals. Although caging conditions influence the cholesterol and triglyceride response to the atherogenic diet (p<.05), light cycle photoperiod seems to exert a greater effect (p<.005). In conclusion, photoperiod length dramatically affects diet-induced plasma lipid concentrations in young male F1B hamsters, and thus needs be considered in experimental designs of animal-housed lipid research.

Aging↗

PubMed2001

Impact of hydrogenated fat on high density lipoprotein subfractions and metabolism.

Relative to saturated fatty acids, trans-fatty acids/hydrogenated fat-enriched diets have been reported to increase low density lipoprotein (LDL) cholesterol levels and either decrease or have no effect on high density lipoprotein (HDL) cholesterol levels. To better understand the effect of trans-fatty acids/hydrogenated fat on HDL cholesterol levels and metabolism, 36 subjects (female, n = 18; male, n = 18) were provided with each of three diets containing, as the major sources of fat, vegetable oil-based semiliquid margarine, traditional stick margarine, or butter for 35-day periods. LDL cholesterol levels were 155 +/- 27, 168 +/- 30, and 177 +/- 32 mg/dl after subjects followed the semiliquid margarine, stick margarine, and butter-enriched diets, respectively. HDL cholesterol levels were 43 +/- 10, 42 +/- 9, and 45 +/- 10 mg/dl, respectively. Dietary response in apolipoprotein (apo) A-I levels was similar to that in HDL cholesterol levels. HDL(2) cholesterol levels were 12 +/- 7, 11 +/- 6, and 14 +/- 7 mg/dl, respectively. There was virtually no effect of dietary fat on HDL3 cholesterol levels. The dietary perturbations had a larger effect on particles containing apoA-I only (Lp A-I) than apoA-I and A-II (Lp A-I/A-II). Cholesterol ester transfer protein (CETP) activity was 13.28 +/- 5.76, 15.74 +/- 5.41, and 14.35 +/- 4.77 mmol x h(-1) x ml(-1), respectively. Differences in CETP, phospholipid transfer protein activity, or the fractional esterification rate of cholesterol in HDL did not account for the differences observed in HDL cholesterol levels. These data suggest that the saturated fatty acid component, rather than the trans- or polyunsaturated fatty acid component, of the diets was the putative factor in modulating HDL cholesterol response.

Aged↗

PubMed2000

Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3-qter: a genome-wide scan in the Framingham study.

Some studies show that plasma triglyceride (TG) levels are a significant independent risk factor for cardiovascular disease (CVD). TG levels are inversely correlated with high density lipoprotein cholesterol (HDL-C) levels, and their metabolism may be closely interrelated. Therefore, the TG/HDL-C ratio may be a relevant CVD risk factor. Our analysis of families in the Framingham Heart Study gave a genetic heritability estimate for log(TG) of 0.40 and for log(TG/HDL-C) of 0.49, demonstrating an important genetic component for both. A 10 cM genome-wide scan for log(TG) level and log(TG/HDL-C) was carried out for the largest 332 extended families of the Framingham Heart Study (1702 genotyped individuals). The highest multipoint variance component LOD scores obtained for both log(TG) and log(TG/HDL-C) were on chromosome 7 (at 155 cM), where the results for the two phenotypes were 1.8 and 2.5, respectively. The 7q32.3-qter region contains several candidate genes. Four other regions with multipoint LOD scores greater than one were identified on chromosome 3 [LOD score for log(TG/HDL-C) = 1.8 at 140 cM], chromosome 11 [LOD score for log(TG/HDL-C) = 1.1 at 125 cM], chromosome 16 [LOD score for log(TG) = 1.5 at 70 cM, LOD score for log(TG/HDL-C) = 1.1 at 75 cM] and chromosome 20 [LOD score for log(TG/HDL-C) = 1.7 at 35 cM, LOD score for log(TG) = 1.3 at 40 cM]. These results identify loci worthy of further study.

Aged↗

PubMed2000

Absence of linkage for bone mineral density to chromosome 12q12-14 in the region of the vitamin D receptor gene.

Polymorphisms in the region of the gene for the vitamin D receptor (VDR) (chromosome 12q12-14) have been associated with differences in bone mineral density (BMD) in some studies but not in others. Because linkage analysis assesses allele sharing identical-by-descent among relatives instead of the association of a particular allele of an anonymous marker, we have performed a linkage study for bone BMD using microsatellite markers flanking the VDR locus. The present study explores whether or not relatives who share the chromosomal region containing the VDR gene have more similar bone density. Participants in the Framingham Osteoporosis Study (aged 37-89 years) who had undergone BMD testing were used to test for concordance of genotype with phenotype in the hip (femoral neck, Ward's area, trochanter) and lumbar spine (L2-L4) with adjustment for covariates. Multipoint quantitative trait linkage analysis using variance components methods was conducted with microsatellite markers flanking the VDR locus (GATA91H06, GATA5A09, GGAT2G06) in 332 extended families containing 1062 individuals with both bone density measures and marker data. In addition, quantitative trait sib-pair linkage analysis, with a marker (AFM345xf1) in close proximity to the VDR locus, was performed in a second sample of 169 sibships (n = 413), comprising 284 full-sib pairs. Neither analysis revealed evidence for linkage of this region to femoral neck, Ward's area, lumbar spine, and trochanter in age or sex BMI, and height-adjusted bone density measures. Additional adjustment for alcohol intake, caffeine consumption, smoking status, and estrogen supplement (female only) did not alter the results. The present study could not demonstrate linkage of BMD to chromosome 12q12-14. These findings suggest that neither the VDR gene nor other genes at this locus are likely to have a substantial impact upon bone density.

Absorptiometry, Photon↗

PubMed2000

Diet and coronary heart disease: clinical trials.

Dietary intervention trials using coronary heart disease (CHD) mortality and morbidity as endpoints have demonstrated that restriction of dietary total and saturated fat or replacement of the latter with polyunsaturated fatty acids (PUFAs), in particular n-3 PUFAs, is of great benefit with respect to CHD risk. This is likewise the case for intervention trials using angiographic endpoints, with many studies showing that such diets not only retard progression of coronary atherosclerosis but can cause regression as well. The role that antioxidants, such as vitamin E, may play in the development and progression of CHD is less clear. The results of large-scale clinical trials evaluating the effect of vitamin E supplementation on CHD risk do not support the concept that this agent is cardioprotective. The purpose of this report is to review dietary intervention trials that support a direct relationship between diet, lipoproteins, and CHD risk.

Antioxidants↗

PubMed2000

Association of apolipoprotein (Apo)E genotype with plasma apo E levels.

The purpose of this study was to investigate the effects of apolipoprotein (apo) E genotype on plasma apo E levels as well as serum total, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, and glucose values in 734 middle-aged and elderly, female and male subjects. Apo E allele frequencies were similar to those reported in other Caucasian populations. After adjustment for medications, alcohol use, smoking, age, and body mass index, apo E genotype was noted to have significant effects on apo E, total cholesterol, LDL cholesterol, and glucose levels in females, and on apo E, LDL cholesterol, and HDL cholesterol levels, as well as the total cholesterol (TC)/HDL cholesterol ratio in males. Female and male subjects with the apo E4 allele had significantly (P<0.05) lower plasma apo E (25 and 15%) and higher LDL cholesterol levels (5 and 2%), while those with the apo E2 allele had significantly (P<0.05) higher apo E (32 and 27%) and lower LDL cholesterol levels (10 and 10%) than the apo E3/3 group. Moreover, female apo E4 carriers had significantly (P<0.05) lower glucose values (11%) than the apo E3/3 group. These data are consistent with the concept that, in addition to the well known effects of apo E genotype on LDL-C values, this locus plays a very significant role in modulating plasma apo E levels.

Adult↗

PubMed2000

Absence of association between genetic variation in the promoter of the microsomal triglyceride transfer protein gene and plasma lipoproteins in the Framingham Offspring Study.

Microsomal triglyceride transfer protein (MTP) is a lipid transfer protein that is required for the assembly and secretion of very low density lipoproteins (VLDL) by the liver and chylomicrons by the intestine. The common G-493T polymorphism of the MTP promoter has been shown to be associated with decreased plasma LDL-cholesterol and ApoB content of VLDL. The purpose of the present study was, therefore, to investigate the association of this mutation with variations in lipid and apoprotein levels, lipoprotein subclass profiles and coronary heart disease (CHD) risk in a population-based sample of 1226 male and 1284 female Framingham Offspring participants. In men and women, no significant association was found between the G-493T MTP polymorphism and variations of plasma levels of total cholesterol, LDL-cholesterol, apoprotein B, HDL-cholesterol, apoprotein AI and triglycerides. In order to further investigate potential relationships with variations of lipoprotein phenotypes, lipoprotein subclass profiles were measured using automated nuclear magnetic resonance (NMR) spectroscopy. Each NMR profile yielded information on lipid mass of VLDL, LDL, and HDL subclasses. In both genders, there was no significant association between the G-493T polymorphism and variability of lipoprotein subclass distributions or lipoprotein particle size. Furthermore, no significant association was found between the polymorphism of the MTP promoter and prevalence or the age of onset of CHD. Thus, our results suggest that the G-493T mutation in the MTP promoter is unlikely to have significant implications for cardiovascular disease in men and women.

Adult↗