Biomedical subjects

Jean Bergeron

Publications and source records attributed to Jean Bergeron.

66 records · Page 4Linked to original sources

PubMed2002

Characterization of LDL particle size among carriers of a defective or a null mutation in the lipoprotein lipase gene: the Québec LIPD Study.

OBJECTIVE: The objective of the present study was to compare the impact of the null P207L and defective D9N mutations in the LPL gene on LDL particle size among heterozygous carriers. METHODS AND RESULTS: LDL particle size was measured on whole plasma by 2% to 16% non-denaturing polyacrylamide gradient gel electrophoresis in a cohort of 206 heterozygous carriers of either the P207L or the D9N mutation. The P207L carriers (N=88) presented with a more atherogenic lipoprotein-lipid profile compared with the D9N carriers (N=118). Accordingly, LDL particle size was smaller in the P207L carriers than in the D9N subjects (248.8+/- 1.0 vs 254.5+/-1.0 A, P< 0.001), and the difference remained significant after adjustment for plasma triglyceride (TG) levels. The difference in LDL diameter between the P207L and the D9N carriers was 3-fold greater in individuals with plasma TG levels >3.5 mmol/L than in subjects with TG < or =3.5 mmol/L. The factors that statistically contributed to LDL particle size variation in multivariate analyses were plasma TG levels (11.6%) and age (6.4%) in subjects with TG levels < or =3.5 mmol/L and HDL cholesterol levels (15.5%) and the LPL gene mutation (null versus defective, 7.0%) in patients with TG levels >3.5 mmol/L. CONCLUSIONS: These results suggest that the null P207L mutation in the LPL gene has a greater impact on LDL particle size than the defective D9N mutation and that this mutation-specific effect is amplified at greater plasma TG concentrations.

Cohort Studies↗

PubMed2002

Familial aggregation of blood lipid response to exercise training in the health, risk factors, exercise training, and genetics (HERITAGE) Family Study.

BACKGROUND: Fasting levels of plasma lipids and lipoproteins are reported to improve with regular exercise training. However, little is known on whether the training responses are influenced by heritable factors. METHODS AND RESULTS: The lipid profile was assessed in 115 black (224 individuals) and 99 white families (469 individuals), who participated in the HERITAGE Family Study, while in a sedentary state (baseline visit) and after exercise training for 20 weeks (post visit). Variables included total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I, and HDL-C subfractions 2 (HDL2-C) and 3 (HDL3-C). Familial correlations for the training responses (Delta=post-baseline) were significant for most variables, and the percent variance accounted for by familial factors (ie, maximal heritabilities) ranged from 25% to 38%. Exceptions were for higher heritabilities near 60% for DeltaApoB in blacks and DeltaHDL2-C in whites and a lower estimate of zero for DeltaLDL-C in blacks. CONCLUSIONS: Heritable factors in part determine lipid profile responses to regular exercise. Maximal heritabilities were similar across ethnic groups and variables, except for DeltaLDL-C, DeltaApoB, and DeltaHDL2-C. Molecular studies to identify the markers and genes associated with these influences are currently underway.

Adolescent↗

PubMed2002

Association of fibrinogen and lipoprotein(a) as a coronary heart disease risk factor in men (The Quebec Cardiovascular Study).

Fibrinogen has been prospectively found to correlate with coronary heart disease (CHD) but a similar association has not been well established for lipoprotein (a) (Lp(a)). Plasma lipids, Lp(a), and fibrinogen levels were measured in 2,125 men (aged 47 to 76 years) who were free of clinical CHD. During a 5-year follow-up period, 116 first CHD events were documented. Men with CHD were older, smoked more, had a higher prevalence of diabetes, and higher levels of systolic blood pressure, cholesterol, low-density lipoprotein cholesterol, Lp(a), and fibrinogen, and lower plasma high-density lipoprotein cholesterol levels. Only fibrinogen levels in the upper tertile of the distribution compared with the lower tertiles were associated with a significant risk of CHD (adjusted risk ratio 2.5; 95% confidence interval [CI] 1.4 to 4.2; p = 0.0010). Such an association was not observed with Lp(a). To assess a possible relation between fibrinogen and Lp(a) to the risk of CHD events, men were assigned to 1 of 4 groups according to fibrinogen median levels and a Lp(a) cut-off level of 300 mg/L: group 1: fibrinogen < 4.05 g/L and Lp(a) < 300 mg/L; group 2: fibrinogen < 4.05 g/L and Lp(a) > or =300 mg/L; group 3: fibrinogen > or =4.05 g/L and Lp(a) < 300 mg/L; and group 4: fibrinogen > or =4.05 g/L and Lp(a) > or =300 mg/L. Using group 1 as a reference, a significant risk ratio was only documented in group 4 (2.5; 95% CI 1.2 to 5.1; p = 0.0132). In this population, high fibrinogen levels associated with high Lp(a) levels significantly increased the risk of CHD.

Adult↗

PubMed2002

HDL particle size: a marker of the gender difference in the metabolic risk profile.

A low plasma HDL-cholesterol concentration is an important risk factor for coronary heart disease (CHD) and is often accompanied by increased triglyceride concentrations. Women have generally higher HDL-cholesterol and lower triglyceride concentrations and concomitantly are at lower risk of CHD than men. As HDL particle size is a new and potentially important marker of CHD risk, we have examined the potential gender difference in HDL particle size, assessed by nondenaturing 4-30% polyacrylamide gradient gel electrophoresis, in a sample of men (n=231) and women (n=183). Overall, men were characterized by a less favorable lipoprotein--lipid profile, which was accompanied by smaller HDL particle size compared to women. However, when men and women were matched for HDL particle size and compared for their metabolic profile, it was found that both genders were characterized by similar plasma lipoprotein--lipid profile despite the fact that women were characterized by higher levels of total body fat but lower waist girth than men. In summary, HDL particle size is a strong marker of the gender-related difference in the determination of the metabolic risk profile.

Adolescent↗

PubMed2002

Influence of LDL receptor gene mutation and apo E polymorphism on lipoprotein response to simvastatin treatment among adolescents with heterozygous familial hypercholesterolemia.

The efficacy of the inhibitors of HMG CoA reductase shows considerable interindividual variation and intense research has focused in the recent years to identify the genetic loci and environmental factors responsible for this variability. A randomized, double-blind, placebo-controlled clinical trial with simvastatin, an HMG CoA reductase inhibitor, was conducted in 63 adolescents (47 treated versus 17 controls) with heterozygous FH. The patients were grouped according to known low-density lipoprotein (LDL) receptor gene mutation class. After 6 weeks of treatment with 20 mg/d of simvastatin, the mean reduction in plasma LDL-cholesterol in patients with a receptor-negative mutation (n=33) was 39% whereas, in the receptor-defective mutation group (n=14), it was 31% (P=0.01). Multiple regression analyses showed that there was a significant association between the apo E polymorphism and LDL-cholesterol response to simvastatin only among heterozygotes for a receptor-negative mutation. In subjects carrying a receptor-defective mutation, however, we observed that 51% of the variability in LDL-cholesterol response was explained by variations in the dosage of simvastatin expressed in mg/kg/day (P=0.0028). There was no significant association between LDL-cholesterol response and the dosage of simvastatin among heterozygotes for a receptor-negative mutation. The results of the present study have shown that the contribution of apo E polymorphism and the dosage of simvastatin to the LDL-cholesterol responsiveness is influenced by the nature of the LDL receptor gene mutation.

Adolescent↗

PubMed2002

Visceral obesity and hyperinsulinemia modulate the impact of the microsomal triglyceride transfer protein -493G/T polymorphism on plasma lipoprotein levels in men.

The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride levels, low high-density lipoprotein-cholesterol concentration and alterations in low-density lipoprotein (LDL) composition and concentration. A functional, non-coding microsomal triglyceride transfer protein (MTP) -493G/T polymorphism of the microsomal triglyceride transfer protein gene has been related to variations in LDL-cholesterol levels. To study the effect of the MTP -493G/T polymorphism on lipoprotein levels in visceral obesity and hyperinsulinemia, a total of 227 men were assigned into two groups on the basis of their MTP -493G/T polymorphism, including 121 GG homozygotes and 105 carriers of the T allele (92 GT and 13 TT). The two genotypic groups did not differ for their physiological characteristics nor for lipoprotein--lipid profiles, before and after adjustment for age. However, GG homozygotes were characterized by higher fasting insulin levels than carriers of the T allele (P<0.05). When the two genotypic groups were further divided on the basis of their visceral adipose tissue (AT) accumulation, assessed by computed tomography, we observed that T allele carriers with low levels of visceral AT (<130 cm(2)) had decreased plasma total cholesterol and LDL-apolipoprotein B (LDL-apoB) levels compared to viscerally obese men (P=0.035 and P=0.0001, respectively). Among GG homozygotes, no significant difference were observed. Although not significant, T allele carriers characterized by visceral obesity tended to have smaller, denser LDL particles than T allele carriers characterized by a low accumulation of visceral AT. When subjects were divided on the basis of their fasting insulin levels, it appears that hyperinsulinemic men were characterized by a deteriorated lipoprotein--lipid profile when they were carriers of the T allele compared to normoinsulinemic men. In summary, visceral obesity and hyperinsulinemia modulate the impact of the MTP -493G/T polymorphism on plasma total cholesterol and LDL-apoB levels, as well as on LDL peak particle diameter.

Abdomen↗

PubMed2002

Determinants of HDL particle size in patients with the null (P207L) or defective (D9N) mutation in the lipoprotein lipase gene: the Québec LipD Study.

The aim of the present study was to examine the impact of the defective D9N and the null P207L mutations in the lipoprotein lipase (LPL) gene on high density lipoprotein (HDL) particle size in relation to specific environmental factors such as obesity, gender and menopausal status. Analyses were carried out in 118 heterozygous carriers of the D9N mutation and 88 heterozygous for the P207L mutation. HDL particle size was measured on whole plasma by non-denaturing 4-30% polyacrylamide gradient gel electrophoresis. Although carriers of the P207L mutation presented a more deteriorated lipoprotein-lipid profile compared with carriers of the D9N mutation, there was no difference in HDL particle size between the P207L and D9N carriers (81.9+/-4.5 vs. 82.7+/-4.4 A, respectively, P=0.2). Multivariate analyses indicated that waist circumference (P=0.001) and HDL cholesterol levels (P<0.001) were independent predictors of HDL particle size among carriers of the defective D9N mutation. On the other hand, gender (P=0.03), plasma cholesterol (P=0.01) and TG (P=0.04) levels were significant predictors of HDL particle size among carriers of the null P207L mutation in multivariate analyses. These results suggest that the nature of the mutation in the LPL gene modifies the relationship of HDL particle size to other metabolic variables and secondary factors such as abdominal obesity and gender.

Adult↗

PubMed2002

Effects of prednisone withdrawal on the new metabolic triad in cyclosporine-treated kidney transplant patients.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality after renal transplantation. Prednisone (Pred) maintenance therapy is associated with risk factors for atherosclerosis. Therefore, we were interested in quantifying the effects of Pred withdrawal on body weight and waist circumference as well as on metabolic markers of coronary heart disease risk. METHODS: Twenty-six cyclosporine-treated renal transplant patients (13 men and 13 women) were evaluated before and after at least 11 months (16 +/- 2.9 months) of Pred withdrawal. A complete fasting lipoprotein-lipid profile as well as anthropometric measurements were obtained from each patient. RESULTS: Pred withdrawal was associated with a 6.0% reduction of body weight (-4.34 +/- 5.40 kg; P < 0.05) and with a 7.7% decrease in waist girth (-7.13 +/- 5.75 cm; P < 0.005) in women, whereas no change in these variables were observed in men. In both genders, plasma low-density lipoprotein (LDL) cholesterol and triglyceride concentrations were unaffected by Pred withdrawal, whereas plasma high-density lipoprotein (HDL) cholesterol levels decreased by 14.0% in women (-0.22 +/- 0.22 mmol/L; P < 0.005) and 22.0% in men (-0.36 +/- 0.28 mmol/L; P < 0.005). Pred withdrawal was associated with a significant reduction in plasma apolipoprotein B concentrations in both women (-0.28 +/- 0.15 g/L; -24.6%; P < 0.0001) and men (-0.22 +/- 0.19 g/L; -20.5%; P < 0.005). A significant reduction in fasting insulin was observed in both women (-27.8 +/- 27.9 pmol/L; -25.3%; P < 0.005) and men (-25.0 +/- 32.8 pmol/L; -21.4%; P < 0.05), whereas the LDL peak particle size was unaffected by Pred withdrawal. CONCLUSIONS: Pred withdrawal modifies several anthropometric and metabolic cardiovascular risk factors in renal transplant patients. Furthermore, female patients may derive further benefits of Pred withdrawal resulting from the concomitant loss of body weight and abdominal fat.

Anti-Inflammatory Agents↗

PubMed2002

Evidence for impaired lipolysis in abdominally obese men: postprandial study of apolipoprotein B-48- and B-100-containing lipoproteins.

BACKGROUND: Abdominal obesity has been associated with postprandial hypertriglyceridemia. The contribution of intestinally and hepatically derived lipoproteins to this exaggerated postprandial lipemic response is not known. OBJECTIVE: We examined the associations between body fatness, fat distribution, and postprandial apolipoprotein (apo) B-48 and apo B-100 concentrations measured in triacylglycerol-rich lipoproteins (TRLs). DESIGN: Dietary fat tolerance was investigated in 50 men aged 28-67 y. The subjects were given a test meal containing 60 g fat/m(2) body surface area and providing 64% of energy from fat, 18% from carbohydrates, and 18% from protein. The meal provided 7524-9196 kJ, depending on body surface area. Blood samples were collected every 2 h over an 8-h period. RESULTS: The increase in plasma triacylglycerol after the meal resulted from increases in both apo B-48- and apo B-100-containing lipoproteins. The apo B-100 concentration was the strongest contributor (R(2) = 69.6%, P = 0.0001) to postprandial triacylglycerol in total TRLs; the postprandial increase in triacylglycerol was best predicted by the apo B-48 concentration (R(2) = 32.7%, P = 0.0001). Visceral abdominal fat was significantly associated with high postprandial TRL apo B-48 and apo B-100 concentrations (r = 0.30-0.44, P < 0.05). After the meal, the apo B-100 concentration in small TRLs decreased in 12 subjects. These men showed features of the insulin resistance-dyslipidemic syndrome, including more visceral fat (P = 0.07) and an altered fasting metabolic profile. CONCLUSION: A lower lipolytic capacity may contribute to the exaggerated and prolonged postprandial lipemia among abdominally obese men.

Adult↗

PubMed2002

Prevalence of 'hypertriglyceridemic waist' in men who participated in the Quebec Health Survey: association with atherogenic and diabetogenic metabolic risk factors.

BACKGROUND: A triad of metabolic markers (high insulin and apolipoprotein B levels, and small, dense, low density lipoprotein particles) is associated with a substantially increased risk of coronary artery disease (CAD) in men. Also, the simultaneous presence of an elevated waist circumference (90 cm or greater) and moderate hypertriglyceridemia (triglyceride concentration 2.0 mmol/L or higher) in men has been shown to be associated with this atherogenic metabolic triad, with a probability of more than 80%. OBJECTIVES: To quantify the prevalence of the 'hypertriglyceridemic waist' phenotype in a sample of adult men and to compare the metabolic risk profile of nondiabetic men with hypertriglyceridemic waist with the CAD risk profile of patients with type 2 diabetes. METHODS: The sample of people who participated in the Quebec Health Survey was used to obtain representative data on the prevalence and distribution of cardiovascular disease risk factors in the Quebec population. Fasting plasma lipoprotein-lipid, insulin and glucose concentrations were measured, and anthropometric measurements were taken in a sample of 907 men. RESULTS: Among men who participated in the Quebec Health Survey, 19% had an elevated waist circumference (90 cm or greater) plus elevated triglyceride levels (2.0 mmol/L or higher). Men with this hypertriglyceridemic waist phenotype were characterized by the highest values for fasting plasma insulin, and the highest total cholesterol to high density lipoprotein cholesterol ratios. They also displayed a metabolic risk profile that was deteriorated to the same extent as that of men with diabetes who had participated in the survey. CONCLUSIONS: The results of the the present study of men who participated in the Quebec Health Survey provide further evidence that the simultaneous measurement and interpretation of waist circumference and fasting triglyceride concentrations may improve the physician's ability to identify abdominally obese men with atherogenic and diabetogenic profiles. Furthermore, this high risk clinical phenotype is highly prevalent (about 20%) among adult men.

Abdomen↗

PubMed1999

Comparison of two techniques for measurement of visceral adipose tissue cross-sectional areas by computed tomography.

Most computed tomography (CT) scanners used today are able to accurately measure adipose tissue (AT) areas at any site of the body. However, first generation CT scanners used by some medical centers are not equipped with appropriate software allowing the measurements of AT areas. The aim of this study was to validate a technique of AT area measurements independent from CT scanner software. Abdominal AT areas were recorded with CT in a sample of 30 men. Areas were thereafter calculated using the standard CT software technique. Total and visceral AT areas were then remeasured using another technique for which X-ray film of each subject's scan was analysed by a system completely independent from the CT scanner (imaging densitometer and NIH image analysis software). Correlations between measurements obtained with the two techniques were very strong for both total (n = 0.99; SEE = 11.7 cm(2)) and visceral AT areas (r = 0.99; SEE = 5.3 cm(2)). Values obtained with the image analysis method were generally higher than with the conventional CT software technique (cross-sectional areas of AT were overestimated by 4.7% for total abdominal and 8.5% for visceral AT respectively). In conclusion, the results indicate that measurements obtained with this image analysis technique would be adequate to correctly rank subjects according to levels of total or visceral AT areas. However, since this method appears to slightly overestimate AT areas, a standardized correction should be performed before comparing subjects with AT areas measured with this technique to subjects whose AT areas have been obtained with the conventional CT software technique. Am. J. Hum. Biol. 11:61-68, 1999. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗

PubMedDate not supplied

Influences of the PPAR alpha-L162V polymorphism on plasma HDL(2)-cholesterol response of abdominally obese men treated with gemfibrozil.

PURPOSE: The effect of gemfibrozil is mediated by the activation of peroxisome proliferator-activated receptor alpha (PPAR alpha). The objective of this study was to determine whether the lipid response to gemfibrozil therapy is influenced by the PPAR alpha-L162V polymorphism. METHODS: Sixty-three abdominally obese men were randomly assigned to a 6-month-intervention program with either receiving a placebo (N = 31) or gemfibrozil (N = 32). RESULTS: In response to gemfibrozil therapy, L162-homozygotes exhibited a 5.5% increase in high-density lipoprotein 2 cholesterol (HDL(2)-C) levels compared with a 50.0% increase among carriers of the V162 allele (P = 0.03). CONCLUSION: These results suggest that the HDL(2)-C response to gemfibrozil is modulated by the PPAR alpha-L162V polymorphism.

Abdomen↗