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*Coronary Artery Disease
*Nutrition
*Obesity
*Obesity in Children
The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 6 2923-2927
Copyright © 2004 by The Endocrine Society

Low-Density Lipoprotein Particle Size and Its Regulatory Factors in School Children

Tadao Shimabukuro, Makoto Sunagawa and Takao Ohta

Department of Pediatrics, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0125, Japan

Address all correspondence and requests for reprints to: Dr. Takao Ohta, Department of Pediatrics, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0125 Japan. E-mail: tohta{at}med.u-ryukyu.ac.jp.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Small low-density lipoprotein (LDL) particles are more atherogenic than larger LDL particles. To help prevent atherosclerotic coronary heart diseases, it may be useful to understand risk factors during childhood. In the present study, we evaluated LDL size and its relationship to other risk factors for atherosclerotic coronary heart disease. LDL size was measured by 2–15% gradient gel electrophoresis in 586 Japanese children (316 boys and 270 girls). Plasma lipids, apolipoproteins (apo), glucose, and insulin were also determined by conventional methods.

Pattern B (LDL size < 25.5 nm) was found in 10.8% of boys and 4.4% of girls. Children with pattern B had a higher body mass index (BMI) and insulin resistance and a more atherogenic lipoprotein profile [higher triglycerides, higher apoB, and lower high-density lipoprotein cholesterol (HDL-C)] than children with pattern A (LDL size >= 25.5 nm). BMI, insulin resistance, and plasma concentrations of triglycerides, glucose, and insulin decreased and plasma concentrations of HDL-C and apoA-I increased as LDL size increased. HDL-C and insulin in boys, and BMI, HDL-C, and apoA-I in girls predicted 22.9 and 28.1% of the variability of LDL size, respectively.

LDL size was correlated with BMI and plasma concentrations of HDL-C, apoA-I, and insulin. Although the contribution of these parameters to LDL size in children was less than that in adults, improvement of these parameters by changes in lifestyle might be important for preventing the development of atherosclerosis even in children.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
PLASMA LEVELS OF low-density lipoprotein (LDL) cholesterol (LDL-C) are positively associated with the risk for coronary heart disease (CHD) (1, 2). However, several studies have shown that 30–40% of CHD patients have normal LDL-C levels (< 130 mg/dl) (3, 4, 5). LDL particles vary in size and hydration density (6, 7). Several LDL subfractions can be identified on gradient gel electrophoresis. Among these LDL subfractions, small LDL particles possess a lower binding affinity for cellular LDL receptor and are more easily oxidized in vitro (8, 9, 10, 11). These data suggest that small LDL particles are atherogenic because their lower binding affinity for LDL receptor reflects a longer plasma residence time for them to be oxidized and taken up by macrophages in extravascular spaces. In accordance with these in vitro data, several case-control studies have indicated that smaller LDL particles are predominant in a high proportion of CHD patients, even those with normal LDL-C levels (12, 13, 14, 15). Subjects with small, dense LDL have a 3-fold greater CHD risk (16). LDL particle size is associated with plasma triglyceride (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), and fractional esterification rate in HDL (17, 18). In addition, age, sex, body fat, insulin resistance, and environmental (diet etc.) and genetic factors have been reported to affect LDL particle size (14, 19, 20, 21).

As previously mentioned, the relationships between LDL size and other risk factors for CHD have been extensively studied in adults. However, the relationships in children are not well understood. The initial stage of atherosclerosis begins in childhood and progresses from fatty streaks to raised lesions in adolescence and young adulthood (22, 23). Therefore, it is rational to investigate LDL size and factors influencing LDL size in children. In the present study, the relationships between LDL size and other parameters that are known as risk factors for CHD in adults were investigated in 586 Japanese children.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

The present study was approved by the Review Board of the University of the Ryukyus. We studied 586 Japanese children (316 boys and 270 girls), between the ages of 7 and 12 yr, who underwent screening for lifestyle-related diseases in Okinawa, Japan. Body mass index (BMI) was calculated as weight (kilograms) divided by height squared (meters2). None of the children who were studied were receiving therapy for weight reduction or drugs to affect lipid metabolism. Venous blood was drawn after an overnight fast. Informed consent was obtained from the parents of all of the children.

Laboratory measurements

LDL size was evaluated by electrophoresis in nondenaturing polyacrylamide gradient gels on precast MULTIGEL-LP (2–15%) according to the procedure specified by the manufacturer (Daichi Pure Chemicals CO., LTD, Tokyo, Japan). Standards used for size calibration included latex beads (37 nm; Dow Chemical Company, Midland, MI) and high-molecular-weight standards (Pharmacia, Uppsala, Sweden). The stained gels were scanned with a laser scanning densitometer to provide a quantitative measurement of the size of the peak and its distance from the origin. Particle diameter was calculated from a plot of the log of the known diameters of the standards (latex beads, 37 nm; thyroglobulin, 17.0 nm; apoferritin, 12.2 nm) on the y-axis against their positions from the origin of the gel on the x-axis. LDL size was classified as pattern A (size >= 25.5 nm) or pattern B (size < 25.5 nm). Plasma concentrations of total cholesterol (TC), TG, and HDL-C were analyzed using an autoanalyzer and enzymatic methods or by selective precipitation using sodium phosphotungstate and magnesium chloride (24, 25). LDL-C was calculated as TC – (HDL-C + TG/5). Apolipoproteins (apo; A-I, A-II, and B) were measured by the turbidity immunoassay method (26). Insulin resistance (homeostasis model of assessment ratio) was calculated using the homeostasis model approximation index, which correlates well with the results of both hyperinsulinemic euglycemic clamp and the intravenous glucose tolerance test, by the following formula: insulin resistance = fasting glucose (mg/dl) x insulin (µU/ml)/405 (27).

Statistical evaluation

Differences between two groups were determined by the Mann-Whitney U test. Differences among subjects with small, medium, and large LDL (tertiles of LDL size) were determined by the Kruskal-Wallis test. Tertiles of LDL size were compared with Scheffé’s multiple comparison test. A stepwise multiple regression analysis was performed by entering the independent variable with the highest partial correlation coefficient at each step until no variable remained with an F value of >= 4. Group differences or correlations with P < 0.05 were considered to be statistically significant. All statistical analyses were performed using Stat View J-5.0 software (SAS Institute Inc., Cary, NC).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The clinical and chemical characteristics of the 586 children are summarized in Table 1Go. Significant gender-related differences were found in LDL size, BMI, plasma concentrations of glucose, apoA-I, and apoA-II, and insulin resistance. Therefore, we separated the data for boys and girls in the following analysis.


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  		TABLE 1. Clinical and chemical data

 
Pattern B was seen in 10.8% of boys and 4.4% of girls. If obese children (BMI >= 21 kg/m2) were omitted, the prevalence in nonobese children was 6.1% in boys and 2.1% in girls (a BMI of 21 kg/m2 in our study subjects was equivalent to +20% of ideal body weight in Japanese school children). As shown in Table 2Go, plasma concentrations of glucose, insulin, TG, and apoB in children with pattern B were significantly higher than those in children with pattern A. Plasma concentrations of TC and LDL-C were higher in pattern B than in pattern A children, but these differences were significant only in boys. The plasma concentrations of HDL-C and apoA-I in pattern B children were significantly lower than those in pattern A children, but the difference of apoA-I was significant only in girls. BMI and insulin resistance were significantly higher in children with pattern B than in children with pattern A.


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  		TABLE 2. Clinical and chemical data on children with pattern A and pattern B

 
To understand the relation of LDL size to lipids and other parameters in more detail, subjects were divided into tertiles based on LDL size (boys: small tertile, LDL size < 26.3 nm; medium tertile, 26.3 nm <= LDL size <= 27.2 nm; and large tertile, LDL size > 27.2 nm; girls: small tertile, LDL size < 26.7 nm; medium tertile, 26.7 nm <= LDL size <= 27.6 nm; and large tertile, LDL size > 27.6 nm). As shown in Table 3Go, there were significant graded relationships between tertiles of LDL size and parameters (BMI, HDL-C, glucose, insulin, insulin resistance, TG, and apoA-I) in boys. However, significance of parameters other than BMI and HDL-C were found between small and medium and/or between small and large tertiles. In girls, there were significant graded relationships between tertiles of LDL size and parameters (BMI, glucose, insulin, insulin resistance, TG, HDL-C, and apoA-I), but significance was only found between small and medium and/or between small and large tertiles (Table 4Go). Because each of these parameters can potentially contribute directly to LDL size, we performed a stepwise multiple regression analysis with LDL size as the dependent variable and the other parameters as independent variables (calculated parameters were excluded; model I: independent parameters exclude BMI, glucose, and insulin; model II: independent parameters include all uncalculated parameters listed in Table 2Go). In model I analysis (step 1), HDL-C was most significantly associated with LDL size and accounted for 16 and 18.4% of the variability of LDL size in boys and girls, respectively (Table 5Go). apoA-I in boys and TG in girls had a small additional effect (2.5% in boys and 2.6% in girls; step 2). In model II analysis, HDL-C in boys and BMI in girls had the most significant association with LDL size and accounted for 15.9 and 18.7% of the variability of LDL size in boys and girls, respectively. Insulin in boys and HDL-C and apoA-I in girls had additional effects. All of these parameters accounted for 22.9 and 28.1% of the variability of LDL size in boys and girls, respectively.


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  		TABLE 3. Clinical and chemical data on boys with different LDL size particles (in tertiles)

 

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  		TABLE 4. Clinical and chemical data on girls with different LDL size particles (in tertiles)

 

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  		TABLE 5. Stepwise multiple regression analysis of correlates of LDL particle size

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study demonstrates the following: 1) the prevalence of pattern B is 10.8% in boys and 4.4% in girls; 2) children with pattern B have higher BMI and insulin resistance and a more atherogenic lipoprotein profile (higher TG, higher apoB, and lower HDL-C) than children with pattern A; 3) BMI, glucose, insulin, insulin resistance, HDL-C, apoA-I, and TG change as a function of the LDL size tertile; and 4) HDL-C and insulin in boys and BMI, HDL-C, and apoA-I in girls can predict 22.9 and 28.1% of the variability of LDL size, respectively.

To date, very limited information is available on LDL size in children (18, 28, 29, 30, 31, 32). With respect to gender differences of LDL size, Freedman et al. (31) also found gender differences in children. Studies in adults have reported that there is a significant gender difference in LDL size, demonstrating that women have larger LDL particles than men (32, 33). Although the underlying mechanism is not clear, differences in visceral fat accumulation and TG catabolism between men and women appear to be responsible for this gender difference (32, 33). In the present study, even after adjusting for BMI and the plasma concentration of TG, a gender difference is seen in our subjects. Thus, further studies are needed to understand the gender difference in children. Arisaka et al. (29) reported that the prevalence of small dense LDL (pattern B) was 9.3% in Japanese school children aged 7–13 yr, and Steinbeck et al. (30) also reported that the prevalence of pattern B was 7.5% in Australian children aged 6.0–9.9 yr. These results are not so different from our present data. In adults, the prevalence of pattern B was 31–44% in the general population in the United States (13, 34), whereas the prevalence in Japan was 10–34.7% (35, 36). In either case, the prevalence of pattern B in children appears to be lower than that in adults. However, as in adults, children with pattern B had more risk factors (atherogenic lipoprotein profile, adiposity, and insulin resistance) for CHD than children with pattern A.

With respect to the correlates of LDL size in children, we previously reported positive associations with HDL-C, apoA-I, and fractional esterification rate in HDL, and a negative association with TG, although the number of subjects studied was small (18). In the present study, we confirmed the previous data and found that BMI, insulin resistance, and plasma concentrations of apoB, glucose, and insulin are also linked to LDL size in children. These findings are similar to those in adults (14, 17, 18, 19, 20, 21). In adults, LDL size and plasma concentrations of TG and HDL-C are closely interrelated, and 50–67% of the variance in plasma LDL size can be explained by plasma concentrations of TG and HDL-C (17, 37). Thus, it is generally accepted that the presence of small LDL could reflect metabolic changes in TG-rich lipoproteins or HDL. It is of interest that HDL-C and insulin for boys and BMI, HDL-C, and apoA-I for girls are independent predictors of LDL size in children. The plasma concentration of TG is not a significant predictor of LDL size in boys and a minor predictor in girls after excluding BMI, glucose, and insulin for analysis (model I). This may be attributable to a nonlinear association between the plasma concentration of TG and LDL size (38). LDL size was affected by plasma TG when the concentration of TG exceeded 1.5 mmol/liter (133 mg/dl) (39). The mean plasma TG concentration in our subjects was lower than this level. In contrast to plasma TG, HDL-C was an independent predictor of LDL size in children (analysis of models I and II). Taken together, these data suggest that correlates of LDL size in children are similar to those in adults, but the effects of each correlate on LDL size in children are much different from those in adults. Furthermore, in the present study, BMI and chemical parameters explained 22.9–28.1% of the variation in LDL size. These values are much lower than those in adults (50–67%). Based on twin studies, it has been reported that one third to half of the variation in LDL size can be attributed to genetic influences (40, 41). However, genetic factors are constant in children and adults. Thus, the lower predictive value suggests that different environmental factors between children and adults, such as body size and lifestyle, may have a great influence on LDL size (children are usually leaner than adults).

In conclusion, LDL size was correlated with BMI and many chemical parameters. Although the contribution of these parameters to LDL size in children was less than that in adults, improvement of these parameters by changes in lifestyle might be important for preventing the development of atherosclerosis in children.

Study limitation

As mentioned, LDL size is influenced by both genetic and environmental factors. Japanese children rarely drink alcohol or smoke and usually exercise regularly at school. Thus, the effects of environmental and genetic factors on LDL size and their implications in Japanese children may be different from those in other countries and other ethnic groups. Thus, our present results may not be generalized before similar studies are performed in other countries and other ethnic groups.


   Footnotes
 
This work was supported by Health Sciences Research Grants (Research on Specific Diseases) from the Ministry of Health, Labour and Welfare and by Grant in Aid 13470166 for Scientific Research (B) from The Ministry of Education, Science, Sports and Culture.

Abbreviations: apo, Apolipoprotein; BMI, body mass index; CHD, coronary heart disease; HDL, high-density lipoprotein; HDL-C, high-density lipoprotein cholesterol; LDL, low-density lipoprotein; TC, total cholesterol; TG, triglyceride.

Received October 20, 2003.

Accepted February 20, 2004.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Kannel WB, Castelli WP, Goldon T, McNamara PM 1971 Serum cholesterol, lipoproteins and the risk of coronary heart disease. Ann Intern Med 74:1–12
  2. Castelli WP, Garrison RJ, Wilson PWF, Abbott RD, Kalousdian S, Kannel WB 1986 Incidence of coronary heart disease and lipoprotein cholesterol levels: The Framingham Heart Study. JAMA 256:2835–2838[Abstract]
  3. Hamsten A, Walldius G, Szamosi A, Dahlen G, de Faire U 1986 Relationship of angiographically defined coronary artery disease to serum lipoproteins and apolipoproteins in young survivors of myocardial infarction. Circulation 73:1097–1110[Abstract/Free Full Text]
  4. Nieminen MS, Mattila KJ, Aalto-Setala K, Kuusi T, Kontula K, Kauppinen-Makelin R, Ehnholm C, Jauhiainen M, Valle M, Taskinen MR 1992 Lipoproteins and their genetic variation in subjects with and without angiographically verified coronary artery disease. Arterioscler Thromb 12:58–69[Abstract/Free Full Text]
  5. Genest Jr JJ, McNamara JR, Salem DN, Schaefer EJ 1991 Prevalence of risk factors in men with premature coronary artery disease. Am J Cardiol 67:1185–1189[CrossRef][Medline]
  6. Krauss RM, Burke DJ 1982 Identification of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res 23:97–104[Abstract]
  7. Shen MMS, Krauss RM, Lindgren FT, Forte TM 1981 Heterogeneity of serum low density lipoproteins in normal human subjects. J Lipid Res 22:236–244[Abstract]
  8. Dejager S, Bruckert E, Chapman MJ 1993 Dense low density lipoprotein subspecies with diminished oxidative resistance predominate in combined hyperlipidemia. J Lipid Res 34:295–308[Abstract]
  9. Tribble DL, Holl LG, Wood PD, Krauss RM 1992 Variations in oxidative susceptibility among six low density subfractions of differing density and particle size. Arteriosclerosis 93:189–199
  10. de Graaf J, Hak-Lemmers HL, Hectors MP, Demacker PN, Hendriks JC, Stalenhoef AF 1991 Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb 11:298–306[Abstract/Free Full Text]
  11. Arad Y, Rumsey SC, Galeano NF, Al-Haideri M, Walsh MT, Marcel YL, Milne RW, Kwiterovich PO, Deckelbaum RJ 1992 LDL has optimal size for maximal binding to the LDL receptor. Circulation 86:I-551
  12. Crouse JR, Parks JS, Schey HM, Kahl FR 1985 Studies of low density lipoprotein molecular weight in human beings with coronary artery disease. J Lipid Res 26:566–574[Abstract]
  13. Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM 1988 Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 260:1917–1921[Abstract]
  14. Campos H, Genest Jr JJ, Blijlevens E, McNamara JR, Jenner JL, Ordovas JM, Wilson PWF, Schaefer EJ 1992 Low density lipoprotein particle size and coronary artery disease. Arterioscler Thromb 12:187–195[Abstract/Free Full Text]
  15. Coresh J, Kwiterovich Jr PO, Smith HH, Bachorik PS 1993 Association of plasma triglyceride concentration and LDL particle diameter, density, and chemical composition with premature coronary artery disease in men and women. J Lipid Res 34:1687–1697[Abstract]
  16. Austin MA, King MC, Vranizan KM, Krauss RM 1990 Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation 82:495–506[Abstract/Free Full Text]
  17. Campos H, Blijlevens E, McNamara JR, Ordovas JM, Posner BM, Wilson PWF, Castelli WP, Schaefer EJ 1992 LDL particle size distribution. Results from the Framingham offspring study. Arterioscler Thromb 12:1410–1419[Abstract/Free Full Text]
  18. Ohta T, Kakiuti Y, Kurahara K, Saku K, Nagata N, Matsuda I 1997 Fractional esterification rate of cholesterol in high density lipoprotein is correlated with low density lipoprotein particle size in children. J Lipid Res 38:139–146[Abstract]
  19. Reaven GM 1993 Role of insulin resistance in human disease (Syndrome X): an expanded definition. Ann Rev Med 44:121–131[CrossRef][Medline]
  20. Campos H, Willett WC, Peterson RM, Siles X, Bailey SM, Wilson PWF, Posner BM, Ordovas JM, Schaefer EJ 1991 Nutrient intake comparisons between Framingham and rural and urban Puriscal, Costa Rica. Arterioscler Thromb 11:1089–1099[Abstract/Free Full Text]
  21. Williams PT, Krauss RM 1997 Associations of age, adiposity, menopause, and alcohol intake with low-density lipoprotein subclasses. Arterioscler Thromb Vasc Biol 17:1082–1090[Abstract/Free Full Text]
  22. Strong JP, McGill Jr HC 1962 The natural history of coronary atherosclerosis. Am J Pathol 40:37–49
  23. Stary HC 1989 Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arteriosclerosis 9(Suppl I):I-19–I-32
  24. Burstein M, Scholnick HR, Morfin R 1970 Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 11:583–595[Abstract]
  25. Warnick GR, Nguyen T, Albers AA 1985 Comparison of improved precipitation methods for quantification of high density lipoprotein cholesterol. Clin Chem 31:217–222[Abstract/Free Full Text]
  26. Ikeda T, Shibuya U, Sugiuchi H, Araki S, Uji Y, Okabe H 1991 Automated immunoturbidimetric analysis of six serum apolipoproteins: correlation with radial immunodiffusion assays. J Clin Lab Anal 5:90–95[Medline]
  27. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC 1985 Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419[CrossRef][Medline]
  28. Ohta T, Nishiyama S, Nakamura T, Saku K, Maung KK, Matsuda I 1998 Predominance of large low density lipoprotein particles and lower fractional esterification rate of cholesterol in high density lipoprotein in children with insulin-dependent diabetes mellitus. Eur J Pediatr 157:276–281[CrossRef][Medline]
  29. Arisaka O, Fujiwara S, Yabuta K, Mokuno H, Mitugi Y, Miyake N 1997 Characterization of low-density lipoprotein subclasses in children. Metabolism 46:146–148[CrossRef][Medline]
  30. Steinbeck KS, Bermingham MA, Mahajan D, Baur LA 2001 Low-density lipoprotein subclasses in children under 10 years of age. J Paediatr Child Health 37:550–553[CrossRef][Medline]
  31. Freedman DS, Bowman BA, Otvos JD, Srinivasan R, Berenson GS 2000 Levels and correlates of LDL and VLDL particle sizes among children: the Bogalusa heart study. Atherosclerosis 152:441–449[CrossRef][Medline]
  32. McNamara JR, Campos H, Ordovas JM, Peterson J, Wilson PWF, Schaefer EJ 1987 Effect of gender, age, and lipid status on low density lipoprotein subfraction distribution: results from the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 7:783–790
  33. Carr MC, Hokanson JE, Zambon A, Deeb SS, Barrett PH 2001 The contribution of intraabdominal fat to gender differences in hepatic lipase activity and low/high density lipoprotein heterogeneity. J Clin Endocrinol Metab 86:2831–2837[Abstract/Free Full Text]
  34. Austin MA, King MC, Vranizan KM, Newman B, Krauss RM 1988 Inheritance of low-density lipoprotein subclass patterns: results of complex segregation analysis. Am J Hum Genet 43:838–846[Medline]
  35. Suehiro T, Ohgura T, Sumiyoshi R, Yasuoka N, Nakauchi Y, Kumon Y, Hashimoto K 1995 Relationship of low-density lipoprotein particle size to plasma lipoproteins, obesity, and insulin resistance in Japanese men. Diabetes Care 18:333–338[Abstract]
  36. Mitsugi Y, Mokuno H, Yamaguchi H 1995 The significance of small density lipoprotein as a risk factor for coronary heart disease in no-diabetic and normocholesterolemic subjects. Domyakukouka 22:841–847
  37. Fagerberg B, Hulthe J, Bokemark L, Wikstrand J 2001 Low-density lipoprotein particle size, insulin resistance, and proinsulin in a population sample of 58-year-old men. Metabolism 50:120–124[CrossRef][Medline]
  38. Packard CJ 1999 Understanding coronary heart disease as a consequence of defective regulation of apolipoprotein B metabolism. Curr Opin Lipidol 10:237–244[CrossRef][Medline]
  39. Griffin BA, Freeman DJ, Tait GW, Thomson J, Caslake MJ, Packard CJ, Shepherd J 1994 Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk. Atherosclerosis 106:241–253[CrossRef][Medline]
  40. Austin MA, Newman B, Selby JV, Edwards K, Mayer EJ, Krauss RM 1993 Genetics of LDL subclass phenotypes in women twins: concordance, heritability, and commingling analysis. Arterioscler Thromb 13:687–695[Abstract/Free Full Text]
  41. Lamon-Fava S, Jimenez D, Christian JC, Fabsitz RR, Reed T, Carmelli D, Castelli WP, Ordovas JM, Wilson PW, Schaefer EJ 1991 The NHLBI Twin Study: heritability of apolipoprotein A-I, B and low density lipoprotein subclasses and concordance for lipoprotein (a). Atherosclerosis 91:97–106[CrossRef][Medline]



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