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Journal of Lipid Research, Vol. 44, 986-993, May 2003
Copyright © 2003 by Lipid Research, Inc.

Effect of apoC-III gene polymorphisms on the lipoprotein-lipid profile of viscerally obese men

Charles Couillard^*,, Marie-Claude Vohl^*,, James C. Engert, Isabelle Lemieux, Alain Houde, Natalie Alméras^*,, Denis Prud'homme, André Nadeau^**, Jean-Pierre Després^*,, and Jean Bergeron^1,

^* Department of Food Sciences and Nutrition, Laval University, Sainte-Foy, Québec, Canada, G1K 7P4
Québec Heart Institute, Sainte-Foy, Québec, Canada G1V 4G5
Lipid Research Center, Laval University Medical Research Center, CHUL Pavilion, Sainte-Foy, Québec, Canada G1V 4G2
^** Diabetes Research Unit, Laval University Medical Research Center, CHUL Pavilion, Sainte-Foy, Québec, Canada G1V 4G2
Montréal Genome Center, McGill University Health Center Research Institute, Montréal, Québec, Canada, H3G 1A4
School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ontario, Canada, K1N 6N5

Published, JLR Papers in Press, February 16, 2003. DOI 10.1194/jlr.M300043-JLR200

¹ To whom correspondence should be addressed. e-mail: jean.bergeron{at}crchul.ulaval.ca

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Abdominal visceral adipose tissue (AT) accumulation is associated with an atherogenic metabolic profile that includes increased plasma triglyceride (TG), low HDL cholesterol levels, and an insulin-resistant hyperinsulinemic state. Whereas the apolipoprotein (apo) C-III C3238G gene variant, often referred to as the SstI polymorphism, has been related to variations in plasma TG concentrations, another variation within the insulin responsive element (C-482T) of the apoC-III gene has been associated with greater glucose and insulin responses to an oral glucose tolerance test (OGTT); however, these results were obtained in nonobese individuals. We therefore investigated the effects of three apoC-III gene polymorphisms, namely SstI, C-482T, and T-455C, on fasting plasma lipoprotein-lipid levels and response to a 75 g OGTT in a sample of 122 viscerally obese men (abdominal visceral AT area 130 cm²). Among the three gene variants that were examined, the SstI variation was the only one found to be associated with hypertriglyceridemia. Indeed, S1/S2 heterozygotes (n = 24) were characterized by increased fasting plasma TG concentrations compared with S1/S1 homozygotes (n = 98) (mean ± SD: 3.03 ± 1.58 vs. 2.34 ± 0.95 mmol/l respectively, P < 0.05). The higher TG concentrations in S1/S2 were associated with the presence of smaller, denser LDL particles compared with S1/S1 subjects (LDL peak particle diameter: 24.8 ± 0.5 nm vs. 25.1 ± 0.5 nm respectively, P < 0.05). Furthermore, there was no association between the response to the OGTT and any of the apoC-III gene variants (SstI, T-455C, or C-482T) examined.

Results of the present study support the notion of a hypertriglyceridemic effect associated with the apoC-III SstI polymorphism that could modulate the magnitude of the dyslipidemic state in abdominally obese patients.

Supplementary key words oral glucose tolerance test • high density lipoprotein • very low density lipoprotein • triglycerides

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Apolipoprotein (apo) C-III, a protein produced by the liver, is an essential constituent of VLDL and HDL (1). Considering the inhibitory effect of apoC-III on lipoprotein lipase (LPL) activity and hepatic uptake of lipoproteins (2, 3), apoC-III gene variants have been proposed as being potentially responsible for the occurrence of lipoprotein-lipid profile disturbances. Accordingly, numerous polymorphisms in the apoC-III gene have been identified (4). The first one reported involves the substitution of a cytosine to a guanine in the 3' untranslated region of the gene, which alters a SstI restriction site (5). The prevalence of the rare S2 allele in the white population has been estimated to vary between 0.08 and 0.30 (6–10). The SstI apoC-III gene polymorphism has been associated with altered plasma triglyceride (TG) concentrations (4, 5, 7, 10–20). However, the physiological mechanisms by which this genetic variation leads to an impairment of TG metabolism remain unexplained.

In addition to the SstI, other variations are noted in the promoter region of the apoC-III gene (Fig. 1) . More specifically, the C-482T and T-455C variants are located within an insulin response element (IRE) of the apoC-III gene (21). These two apoC-III promoter polymorphisms have been shown to inactivate a negative IRE located between nucleotides -449 and -490 (21), and are in linkage disequilibrium with the apoC-III SstI polymorphism (22). In addition, variation at the C-482T position has been shown to influence the glucose and insulin response to an oral glucose tolerance test (OGTT), carriers of the C-482T rare allele having significantly elevated glucose and insulin concentrations following the glucose challenge (20).

View larger version (14K): [in this window] [in a new window]   Fig. 1. The apolipoprotein (apo) AI-C-III-AIV gene region.

	MATERIALS AND METHODS

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Subjects
One hundred and twenty two men (mean age ± SD: 44 ± 8 years) with an abdominal visceral AT area 130 cm² were recruited through the media and gave their written consent to participate in the study, which was approved by the Medical Ethics Committee of Laval University. Subjects were all nonsmokers, and those with diabetes, endocrine disorders, or CHD were excluded from the study. None of the subjects was on medication known to affect insulin action or plasma lipoprotein levels.

Anthropometry, body composition, and fat distribution
Body weight and height, as well as waist and hip circumferences, were measured following standardized procedures (28), and the waist-to-hip ratio was calculated. Body density was measured by the hydrostatic weighing technique (29). The mean of six measurements was used in the calculation of percent body fat from body density using the equation of Siri (30). Fat mass was obtained by multiplying body weight by percent body fat. Abdominal visceral and subcutaneous AT accumulations were assessed by computed tomography, which was performed on a Siemens Somatom DRH scanner (Erlangen, Germany) using previously described procedures (31, 32).

DNA analysis
Peripheral venous blood was collected in tubes containing EDTA and kept frozen at -20°C until processing. Total DNA was extracted by a standardized protocol of digestion with proteinase K. A PCR-restriction fragment length polymorphism-based method adapted by Dammerman et al. (19) was used to genotype the apoC-III gene polymorphisms. PCR products were digested with 15 units of SstI enzyme for a minimum of 3 h at 37°C. The resulting fragments were separated according to their size by electrophoresis on 8% nondenaturing polyacrylamide gel. The alleles lacking the restriction site were designated as S1, while those containing the SstI site were designated as S2. C-482T and T-455C variations were determined by the allele-specific oligonucleotide hybridization assay as previously described (19).

Fasting plasma lipoprotein concentrations
Blood samples were obtained in the morning after a 12 h overnight fast. Cholesterol and TG levels were determined in plasma and in lipoprotein fractions by enzymatic methods (Randox Co., Crumlin, UK) using a RA-500 analyzer (Bayer Corporation Inc., Tarrytown, NY), as previously described (33). Plasma VLDLs (d < 1.006 g/ml) were isolated by ultracentrifugation, and the HDL fraction obtained after precipitation of LDL in the infranatant (d > 1.006 g/ml) with heparin and MnCl₂ (34). The cholesterol and TG contents of the infranatant fraction were measured before and after the precipitation step. The cholesterol content of HDL₂ and HDL₃ subfractions was also determined after further precipitation of HDL₂ with dextran sulfate (35). ApoB concentration was measured in plasma by the rocket immunoelectrophoretic method of Laurell (36), as previously described (37). The lyophilized serum standards for apoB measurements were prepared in our laboratory and calibrated with reference standards obtained from the Centers for Disease Control (Atlanta, GA). Plasma apoC-III concentrations were measured by nephelometry (BN-100, Dade-Behering, Marburg, Germany) using polyclonal antibodies against human apoC-III (Kamiya Biomedical Co., Seattle, WA). Intra- and interassay coefficients of variation for this measurement were both 6.0%. LDL particle diameter was assessed by nondenaturating 2–16% PAGE as already described (27, 38).

Postheparin plasma lipase activity
Postheparin LPL and hepatic lipase (HL) activities were also measured on one occasion in subjects after a 12 h overnight fast, 10 min after an intravenous injection of heparin (60 IU/kg body mass). The activities were measured using a modification of the method of Nilsson-Ehle and Ekman (39), as previously described (40), and expressed as nmoles of oleic acid released per ml of plasma per min.

OGTT
A 75 g OGTT was performed in the morning after an overnight fast. Blood samples were collected under EDTA through a venous catheter from an antecubital vein at -15 min, 0 min, 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 150 min, and 180 min for determination of plasma glucose and insulin levels. Plasma glucose was measured enzymatically (41), whereas plasma insulin was measured by radioimmunoassay with polyethylene glycol separation (42).

Statistical analyses
Whereas the SstI polymorphism was determined in all subjects, the T-455C and C-482T variants were determined in 103 and 111 men, respectively. Overall, 102 subjects had information for all three apoC-III gene polymorphisms. Differences between groups were tested for significance by using ANOVA with post-hoc Duncan multiple range tests. All comparisons were adjusted for age. Spearman correlation coefficients (nonparametric variables) were computed in order to study associations between variables. Areas under the curve of glucose and insulin were determined by the trapezoid method. Multiple regression analyses were also performed to estimate the independent contributions of the different apoC-III gene polymorphisms, as well as adiposity, fat distribution, and metabolic variables to the variation in fasting plasma TG concentrations. For statistical purposes and when necessary, variables were log₁₀ transformed, but raw data are presented in tables and figures. In all analyses, a P value of <0.05 was considered statistically significant. All analyses were conducted with the SAS statistical package (SAS Institute, Cary, NC).

	RESULTS

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On average, the 122 subjects were obese as suggested by a mean BMI of 31.2 ± 3.6 kg/m². Men also had high abdominal and visceral fat accumulation as indicated by a waist circumference of 104.4 ± 8.3 cm and an abdominal visceral fat area of 196 ± 49 cm², respectively. Figure 2 shows the distribution of visceral AT accumulations in the 122 men. Allele frequencies of the minor SstI, T-455C, and C-482T alleles in the present group of abdominally obese men were 9.8%, 34.5%, and 26.1%, respectively. Furthermore, distribution of genotypes for all variants in our group of men was not significantly different from the one expected by the Hardy-Weinberg equilibrium.

View larger version (13K): [in this window] [in a new window]   Fig. 2. Distribution of visceral adipose tissue accumulations (measured by computed tomography) in the 122 men.

View larger version (27K): [in this window] [in a new window]   Fig. 3. Fasting plasma triglyceride concentrations in men classified on the basis of the different combinations of apoC-III gene polymorphisms. T,C/C represents men heterozygous or homozygous for the T-455C variant. C,T/T represents men heterozygous or homozygous for the C-482T variant. Values are means ± SEM.

View larger version (22K): [in this window] [in a new window]   Fig. 4. Plasma insulin (A, C, E) and glucose (B, D, F) levels during a 75 g oral glucose tolerance test in abdominally obese men separated on the basis of the SstI, T-455C, and C-482T apoC-III gene polymorphisms. Values are means ± SEM.

	DISCUSSION

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Frequency of the different variants of the apoC-III gene observed in the present study was comparable to the prevalence already reported in the greater Québec City area (43) and other Caucasian populations (13, 20), which suggests that it is unlikely that there is an increased prevalence of carriers of either the apoC-III SstI, T-455C, or C-482T genotypic variations among subjects with high visceral AT accumulation compared with nonobese normolipidemic subjects.

Of all apoC-III gene polymorphisms examined in the present study, only the SstI variant appeared to be associated with plasma TG concentrations. Indeed, we found that the carriers of the S2 allele were characterized by significantly higher TG concentrations compared with S1/S1 subjects. This observation supports the association between hypertriglyceridemia and the apoC-III SstI polymorphism (4, 11). However, we also found that, irrespective of the presence or absence of the SstI polymorphism, viscerally obese subjects were characterized by elevated fasting TG concentrations. Indeed, both groups of subjects had mean TG levels above 2.0 mmol/l, an upper limit to define elevated TG concentrations as recommended by the Canadian Working Group on Hypercholesterolemia and Other Dyslipidemias (44). Thus, it seems unlikely that the hypertriglyceridemic state that characterizes visceral obesity (25, 26) results from a greater proportion of S1/S2 individuals in the viscerally obese population.

The SstI site could be in linkage disequilibrium with other mutations that affect apoC-III levels. It has been shown that five other polymorphic sites in the promoter of the apoC-III gene have a strong allelic association with the SstI polymorphism (19). However, results from two recently published studies suggest that such linkage disequilibrium between the SstI polymorphism and these other apoC-III gene promoter variants (14, 22) does not explain the association between high TG levels and the S2 allele. Indeed, Surguchov et al. (22) showed that, although the minor alleles of six polymorphic sites (positions -935, -641, -630, -625, C-482T, and T-455C) were in strong linkage disequilibrium with each other and with the S2 polymorphic nucleotide, they were unable to detect an association of any specific S2 haplotype with elevated levels of plasma TGs over and above those conferred by the presence of the S2 polymorphic nucleotide alone. This is consistent with our results showing no independent contribution of the T-455C and C-482T polymorphisms to fasting plasma TG levels. Furthermore, in men carrying the minor T-455C or C-482T alleles, only those bearing the S2 allele had TG levels above the 75th percentile (3.1 mmol/l). On the other hand, a strong allelic association has been reported between the SstI site and two variants within the apoC-III gene itself (45). However, no study has yet demonstrated a link between these polymorphic sites and any functional alteration of apoC-III that could explain the proposed association between hypertriglyceridemia and SstI. We cannot exclude the possibility of linkage disequilibrium with others variants from genes located in the apoC-III chromosomal region. For instance, variants in the newly discovered apoA-V gene (46) near the apoC-III gene need to be further investigated and may be revealed as having a significant role in the association between higher TG and the apoC-III SstI polymorphism. In addition, as already proposed, a potential effect of the SstI polymorphism on mRNA stability cannot be excluded (47).

Elevated apoC-III concentrations have been associated with high plasma TG levels through the inhibition of LPL activity and reduction of TG-rich lipoprotein clearance by the liver (2, 3). This is certainly supported by results from our multivariate analyses that showed that the plasma apoC-III level was the strongest predictor of plasma TG concentration in our group of men. Furthermore, to our knowledge, the relationship between the apoC-III gene SstI polymorphism and apoC-III circulating levels has never been documented in viscerally obese individuals. In our study, a trend for higher plasma apoC-III levels was found in S1/S2 men, although the difference with S1/S1 subjects did not reach statistical significance (156 ± 29 vs. 144 ± 36 mg/l, respectively, P = 0.18), probably due to lack of statistical power. Furthermore, as we only measured total plasma apoC-III concentrations, further studies should also be conducted in order to identify a possible contribution of the SstI polymorphism to the distribution of apoC-III in different lipoprotein subclasses e.g., VLDL, LDL, and HDL, which could possibly explain the association between hypertriglyceridemia and the SstI polymorphism. The importance of this kind of information has been recently underlined as Sacks and colleagues (48) showed that the apoC-III concentration in VLDL+LDL, but not in HDL, was an independent predictor of recurrent coronary events. On the other hand, the hypertriglyceridemic state of S1/S2 men compared with S1/S1 subjects may be explained, at least in part, by the lower HL activity in the S2 allele carriers. The significant negative correlations between HL activity and the TG content of LDL (r = -0.41, P < 0.0001) suggest such a possibility. In support of this, S1/S2 men were characterized by higher LDL-TG and HDL-TG levels, while showing lower HL activity compared with S1/S1 subjects. Interestingly, the apoC-III SstI genotype was a weak yet significant predictor of postheparin plasma HL activity (4.9%, P = 0.0474).

The insulin response to an OGTT has been reported to be affected by the apoC-III gene polymorphism (6, 20). In the present study, no difference was found in the glucose or insulin response to the glucose challenge among men carrying the minor allele of either the SstI, T-455C, or C-482T variants. However, it is well known that visceral obesity is associated with disturbances in glucose-insulin homeostasis (49). Whereas Salas et al. (6) and Waterworth et al. (20) studied apparently nonobese individuals, we investigated only viscerally obese men. This discrepancy in subject characteristics between the two studies may account for the difference in the response to the OGTT between carriers versus noncarriers of the SstI, T-455C, or C-482T polymorphism. Possibly, the impact of visceral obesity on glucose-insulin metabolism could be greater than the contribution of the apoC-III gene polymorphism to plasma glucose-insulin homeostasis.

In summary, our results suggest that the apoC-III SstI polymorphism is associated with hypertriglyceridemia in viscerally obese subjects who are already characterized by moderately elevated plasma TG concentrations. As the relationships between fasting TG levels and body fat distribution indices appear to be altered by the presence of the rare S2 allele, and considering that the associations between TG and other metabolic risk profile variables are observed both in S1/S1 and S1/S2 men, we conclude that the etiology of higher TG levels in apoC-III SstI polymorphism carriers appears to be independent of adiposity and abdominal fat accumulation, but that the impact of increased TG concentrations on HDL cholesterol levels and LDL particle size is not affected by the presence of the apoC-III SstI polymorphism, at least in viscerally obese men.

	ACKNOWLEDGMENTS

 
This study was conducted with the financial support of the Canadian Institutes of Health Research (operating grant MT14014 and group grant MGC15187) and by the Québec Heart and Stroke Foundation. C.C., M-C.V., and J.B. are research scholars from the Fonds de la recherche en santé du Québec (FRSQ). J.C.E. is a postdoctoral fellow of the National Institutes of Health. I.L. is a recipient of a studentship from the Heart and Stroke Foundation of Canada. J-P.D. is chair professor of nutrition and lipidology supported by Pfizer, Provigo, and the Foundation of the Québec Heart Institute. The authors would like to thank the staff of the Physical Activity Sciences Laboratory for data collection, and the personnel of the Lipid Research Center for their excellent and dedicated contribution to the study.

Manuscript received January 28, 2003

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

1. Mahley, R. W., T. L. Innerarity, S. C. Rall, Jr., and K. H. Weisgraber. 1984. Plasma lipoproteins: apolipoprotein structure and function. J. Lipid Res. 25: 1277–1294.[Abstract]

2. McConathy, W. J., J. C. Gesquiere, H. Bass, A. Tartar, J. C. Fruchart, and C. S. Wang. 1992. Inhibition of lipoprotein lipase activity by synthetic peptides of apolipoprotein C–III. J. Lipid Res. 33: 995–1003.[Abstract]

3. Ginsberg, H. N., N. A. Le, I. J. Goldberg, J. C. Gibson, A. Rubinstein, P. Wang-Iverson, R. Norum, and W. V. Brown. 1986. Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins C-III and AI. Evidence that apolipoprotein C-III inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo. J. Clin. Invest. 78: 1287–1295.

4. Talmud, P. J., and S. E. Humphries. 1997. Apolipoprotein C–III gene variation and dyslipidaemia. Curr. Opin. Lipidol. 8: 154–158.[CrossRef][Medline]

5. Rees, A., C. C. Shoulders, J. Stocks, D. J. Galton, and F. E. Baralle. 1983. DNA polymorphism adjacent to human apoprotein A-1 gene: relation to hypertriglyceridaemia. Lancet. 1: 444–446.[CrossRef][Medline]

6. Salas, J., S. Jansen, J. Lopez-Miranda, J. M. Ordovas, P. Castro, C. Marin, M. A. Ostos, M. D. Bravo, J. Jimenez-Pereperez, A. Blanco, F. Lopez-Segura, and F. Perez-Jimenez. 1998. The SstI polymorphism of the apolipoprotein C–III gene determines the insulin response to an oral-glucose-tolerance test after consumption of a diet rich in saturated fats. Am. J. Clin. Nutr. 68: 396–401.[Abstract]

7. Tybjaerg-Hansen, A., B. G. Nordestgaard, L. U. Gerdes, O. Faergeman, and S. E. Humphries. 1993. Genetic markers in the apo AI-C-III-AIV gene cluster for combined hyperlipidemia, hypertriglyceridemia, and predisposition to atherosclerosis. Atherosclerosis. 100: 157–169.[CrossRef][Medline]

8. Benlian, P., C. Boileau, N. Loux, D. Pastier, J. Masliah, M. Coulon, M. Nigou, A. Ragab, J. Guimard, and J. B. Ruidavets. 1991. Extended haplotypes and linkage disequilibrium between 11 markers at the APOA1–C3-A4 gene cluster on chromosome 11. Am. J. Hum. Genet. 48: 903–910.[Medline]

9. Xu, C. F., M. N. Nanjee, J. Savill, P. J. Talmud, F. Angelico, M. Del Ben, R. Antonini, B. Mazzarella, N. Miller and S. E. Humphries. 1990. Variation at the apolipoprotein (apo) AI-C-III-AIV gene cluster and apo B gene loci is associated with lipoprotein and apolipoprotein levels in Italian children. Am. J. Hum. Genet. 47: 429–439.[Medline]

10. Ordovas, J. M., F. Civeira, J. Genest, Jr., S. Craig, A. H. Robbins, T. Meade, M. Pocovi, P. M. Frossard, U. Masharani, P. W. Wilson, D. N. Salem, R. H. Ward, and E. J. Schaefer. 1991. Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary artery disease. Atherosclerosis. 87: 75–86.[CrossRef][Medline]

11. Humphries, S. E., R. E. Peacock, and P. J. Talmud. 1995. The genetic determinants of plasma cholesterol and response to diet. In Clinical Endocrinology and Metabolism: International Practice and Research. J. B. Betteridge, editor. Baillère Tindall, London. 797–824.

12. Tas, S., and N. A. Abdella. 1994. Blood pressure, coronary artery disease, and glycaemic control in type 2 diabetes mellitus: relation to apolipoprotein-C-III gene polymorphism. Lancet. 343: 1194–1195.[CrossRef][Medline]

13. Hoffer, M. J., E. J. Sijbrands, F. H. De Man, L. M. Havekes, A. H. Smelt, and R. R. Frants. 1998. Increased risk for endogenous hypertriglyceridaemia is associated with an apolipoprotein C3 haplotype specified by the SstI polymorphism. Eur. J. Clin. Invest. 28: 807–812.[CrossRef][Medline]

14. Shoulders, C. C., T. T. Grantham, J. D. North, A. Gaspardone, F. Tomai, A. de Fazio, F. Versaci, P. A. Gioffre, and N. J. Cox. 1996. Hypertriglyceridemia and the apolipoprotein C-III gene locus: lack of association with the variant insulin response element in Italian school children. Hum. Genet. 98: 557–566.[CrossRef][Medline]

15. Zeng, Q., M. Dammerman, Y. Takada, A. Matsunaga, J. L. Breslow, and J. Sasaki. 1995. An apolipoprotein C-III marker associated with hypertriglyceridemia in Caucasians also confers increased risk in a west Japanese population. Hum. Genet. 95: 371–375.[Medline]

16. Henderson, H. E., S. V. Landon, J. Michie, and G. M. Berger. 1987. Association of a DNA polymorphism in the apolipoprotein C–III gene with diverse hyperlipidaemic phenotypes. Hum. Genet. 75: 62–65.[Medline]

17. Aalto-Setälä, K., K. Kontula, T. Sane, M. Nieminen, and E. Nikkila. 1987. DNA polymorphisms of apolipoprotein A-I/C-III and insulin genes in familial hypertriglyceridemia and coronary heart disease. Atherosclerosis. 66: 145–152.[CrossRef][Medline]

18. Dallinga-Thie, G. M., X. D. Bu, M. van Linde-Sibenius Trip, J. I. Rotter, A. J. Lusis, and T. W. de Bruin. 1996. Apolipoprotein A-I/C-III/A-IV gene cluster in familial combined hyperlipidemia: effects on LDL-cholesterol and apolipoproteins B and C-III. J. Lipid Res. 37: 136–147.[Abstract]

19. Dammerman, M., L. A. Sandkuijl, J. L. Halaas, W. Chung, and J. L. Breslow. 1993. An apolipoprotein C-III haplotype protective against hypertriglyceridemia is specified by promoter and 3' untranslated region polymorphisms. Proc. Natl. Acad. Sci. USA. 90: 4562–4566.[Abstract/Free Full Text]

20. Waterworth, D. M., J. Ribalta, V. Nicaud, J. Dallongeville, S. E. Humphries, and P. Talmud. 1999. ApoC-III gene variants modulate postprandial response to both glucose and fat tolerance tests. Circulation. 99: 1872–1877.[Abstract/Free Full Text]

21. Li, W. W., M. M. Dammerman, J. D. Smith, S. Metzger, J. L. Breslow, and T. Leff. 1995. Common genetic variation in the promoter of the human apo C-III gene abolishes regulation by insulin and may contribute to hypertriglyceridemia. J. Clin. Invest. 96: 2601–2605.

22. Surguchov, A. P., G. P. Page, L. Smith, W. Patsch, and E. Boerwinkle. 1996. Polymorphic markers in apolipoprotein C–III gene flanking regions and hypertriglyceridemia. Arterioscler. Thromb. Vasc. Biol. 16: 941–947.[Abstract/Free Full Text]

23. Björntorp, P. 1992. Abdominal fat distribution and disease: an overview of epidemiological data. Ann. Med. 24: 15–18.[Medline]

24. Kissebah, A. H., and G. R. Krakower. 1994. Regional adiposity and morbidity. Physiol. Rev. 74: 761–811.[Free Full Text]

25. Després, J. P., and B. Lamarche. 1993. Effects of diet and physical activity on adiposity and body fat distribution: Implications for the prevention of cardiovascular disease. Nutr. Res. Rev. 6: 137–159.

26. Lemieux, I., A. Pascot, C. Couillard, B. Lamarche, A. Tchernof, N. Alméras, J. Bergeron, D. Gaudet, G. Tremblay, D. Prud'homme, A. Nadeau, and J. P. Després. 2000. Hypertriglyceridemic waist: A marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men? Circulation. 102: 179–184.[Abstract/Free Full Text]

27. Tchernof, A., B. Lamarche, D. Prud'homme, A. Nadeau, S. Moorjani, F. Labrie, P. J. Lupien, and J. P. Després. 1996. The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care. 19: 629–637.[Abstract]

28. van der Kooy, K., and J. C. Seidell. 1993. Techniques for the measurement of visceral fat: a practical guide. Int. J. Obes. 17: 187–196.[Medline]

29. Behnke, A. R., and J. H. Wilmore. 1974. Evaluation and Regulation of Body Build and Composition. Prentice-Hall, Englewood Cliffs, NJ. 21–27.

30. Siri, W. 1956. The gross composition of the body. Adv. Biol. Med. Phys. 4: 239–280.[Medline]

31. Després, J. P., D. Prud'homme, M. C. Pouliot, A. Tremblay, and C. Bouchard. 1991. Estimation of deep abdominal adipose-tissue accumulation from simple anthropometric measurements in men. Am. J. Clin. Nutr. 54: 471–477.[Abstract/Free Full Text]

32. Ferland, M., J. P. Després, A. Tremblay, S. Pinault, A. Nadeau, S. Moorjani, P. J. Lupien, G. Thériault, and C. Bouchard. 1989. Assessment of adipose tissue distribution by computed axial tomography in obese women: association with body density and anthropometric measurements. Br. J. Nutr. 61: 139–148.[CrossRef][Medline]

33. Moorjani, S., A. Dupont, F. Labrie, P. J. Lupien, D. Brun, C. Gagné, M. Giguère, and A. Bélanger. 1987. Increase in plasma high-density lipoprotein concentration following complete androgen blockage in men with prostatic carcinoma. Metabolism. 36: 244–250.[CrossRef][Medline]

34. Burstein, M., and J. Samaille. 1960. Sur un dosage rapide du cholesterol lié aux - et ß-lipoprotéines du sérum. Clin. Chim. Acta. 5: 609.[CrossRef][Medline]

35. Gidez, L. I., G. J. Miller, M. Burstein, S. Slagle, and H. A. Eder. 1982. Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure. J. Lipid Res. 23: 1206–1223.[Abstract]

36. Laurell, C. B. 1966. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal. Biochem. 15: 45–52.[CrossRef][Medline]

37. Avogaro, P., G. B. Bon, G. Cazzolato, and G. B. Quinci. 1979. Are apolipoproteins better discriminators than lipids for atherosclerosis? Lancet. 1: 901–903.[Medline]

38. Lemieux, I., C. Couillard, A. Pascot, N. Bergeron, D. Prud'homme, J. Bergeron, A. Tremblay, C. Bouchard, P. Mauriège, and J. Després. 2000. The small, dense LDL phenotype as a correlate of postprandial lipemia in men. Atherosclerosis. 153: 423–432.[CrossRef][Medline]

39. Nilsson-Ehle, P., and R. Ekman. 1978. Specific assays for lipoprotein lipase and hepatic lipase activities of post-heparin plasma. In Protides of Biological Fluids. H. Peeters, editor. Pergamon Press, Oxford. 243–246.

40. St-Amand, J., S. Moorjani, P. J. Lupien, D. Prud'homme, and J. P. Després. 1996. The relation of plasma triglyceride, apolipoprotein B, and high-density lipoprotein cholesterol to postheparin lipoprotein lipase activity is dependent on apolipoprotien E polymorphism. Metabolism. 45: 261–267.[CrossRef][Medline]

41. Richterich, R., and H. Dauwalder. 1971. Zur bestimmung des plasmaglukosekonzentration mit der hexokinase-glucose-6-phosphatase-dehydrogenase-methode. Schweiz. Med. Wochenscher. 101: 615–618.

42. Desbuquois, B., and G. D. Aurbach. 1971. Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J. Clin. Endocrinol. Metab. 33: 732–738.[Medline]

43. Garenc, C., S. Aubert, J. Laroche, F. Rousseau, J. Bergeron, and P. Julien. 2001. Determination of the apoC3 C-482T and SstI allele frequencies in the population of Québec City. Can. J. Cardiol. 17(suppl.C): 192C.

44. Fodor, J. G., J. J. Frohlich, J. J. Genest, Jr., and P. R. McPherson. 2000. Recommendations for the management and treatment of dyslipidemia. Report of the Working Group on Hypercholesterolemia and Other Dyslipidemias. Can. Med. Assoc. J. 162: 1441–1447.[Free Full Text]

45. Xu, C. F., P. Talmud, and S. Humphries. 1994. Three new polymorphisms of the ApoAI-C-III-AIV gene cluster. Mol. Cell. Probes. 8: 331–332.[CrossRef][Medline]

46. Pennacchio, L. A., M. Olivier, J. A. Hubacek, J. C. Cohen, D. R. Cox, J. C. Fruchart, R. M. Krauss, and E. M. Rubin. 2001. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science. 294: 169–173.[Abstract/Free Full Text]

47. Esterbauer, H., E. Hell, F. Krempler, and W. Patsch. 1999. Allele-specific differences in apolipoprotein C–III mRNA expression in human liver. Clin. Chem. 45: 331–339.[Abstract/Free Full Text]

48. Sacks, F. M., P. Alaupovic, L. A. Moye, T. G. Cole, B. Sussex, M. J. Stampfer, M. A. Pfeffer, and E. Braunwald. 2000. VLDL, apolipoproteins B, C-III, and E, and risk of recurrent coronary events in the cholesterol and recurrent events (CARE) trial. Circulation. 102: 1886–1892.[Abstract/Free Full Text]

49. Lemieux, S., and J. P. Després. 1994. Metabolic complications of visceral obesity: Contribution to the etiology of type II diabetes and implications for prevention and treatment. Diabete Metab. 20: 375–393.[Medline]

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