Clinical Chemistry AACC Online Job Center
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 45: 963-968, 1999;
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (13)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Larson, I.
Right arrow Articles by Kreuzer, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Larson, I.
Right arrow Articles by Kreuzer, J.
Related Collections
Right arrow Molecular Diagnostics and Genetics
Right arrow Lipids, Lipoproteins, and Cardiovascular Risk Factors
(Clinical Chemistry. 1999;45:963-968.)
© 1999 American Association for Clinical Chemistry, Inc.

Articles

The Lipoprotein Lipase HindIII Polymorphism: Association with Total Cholesterol and LDL-Cholesterol, but not with HDL and Triglycerides in 342 Females

Ilona Larson1, Michael M. Hoffmann3, Jose M. Ordovas2, Ernst J. Schaefer2, Winfried März3 and Jörg Kreuzer1,a

1 Medizinische Klinik III, Universität Heidelberg, 69115 Heidelberg, Germany.

2 US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111.

3 Abteilung Klinische Chemie, Universität Freiburg, 79106 Freiburg, Germany.
a Address correspondence to this author at: Universität Heidelberg, Innere Medizin III, Bergheimer Strasse 58, 69115 Heidelberg, Germany. Fax 49-6221-565515; e-mail jkreuzer{at}med.uni-heidelberg.de


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Background: Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of core triglycerides in chylomicrons and VLDL.

Methods: We investigated the association between the HindIII polymorphism of the LPL gene and fasting glucose, lipid, and lipoprotein concentrations in 683 Caucasians. We first stabilized the study subjects, using an 8-day diet and exercise intervention program before obtaining blood samples. The use of this standardization period reduced the variance of all glucose and lipid concentrations.

Results: In our study, the HindIII allele frequencies for females and males were 0.29 and 0.34 for H- and 0.71 and 0.66 for H+, respectively. We found in females, but not in males, a significant association between the HindIII genotype and total cholesterol (P = 0.007) and LDL-cholesterol (P = 0.018), with females homozygous for the rare H- allele having the lowest, heterozygotes (H-/+) having intermediate, and women homozygous for the common H+ allele having the highest of each of these lipid traits. With regard to triglycerides, HDL-cholesterol, and glucose, no significant effect of the HindIII genotype was noted in either gender.

Conclusions: These results suggest that in a gender-specific manner, the rare LPL HindIII H- allele has a cholesterol-lowering and, therefore, potentially cardioprotective effect compared with the common H+ allele. © 1999 American Association for Clinical Chemistry


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
The primary function of lipoprotein lipase (LPL)1 is the hydrolysis of the core triglycerides of circulating chylomicrons and VLDL (1). LPL releases monoglycerides and free fatty acids, which are taken up by skeletal muscle or adipose tissue (2)(3). LPL is also believed to enhance the binding of apolipoprotein E-containing lipoproteins to the LDL receptor-related protein, affecting catabolism of chylomicron remnants (4). In addition, during lipolysis, apolipoproteins and phospholipids are transferred from triglyceride-rich lipoproteins to HDL3 particles to form HDL2 particles. This transfer accounts for the positive correlation between postheparin plasma LPL activity and plasma HDL2 concentrations (5). HDL2 particles play a crucial role in "reverse cholesterol transport" by taking up tissue cholesterol and transporting it to the liver for excretion. HDL2 concentrations and the extent of coronary heart disease (CHD) appear to be inversely related (6)(7)(8). Hence, variability of LPL activity may represent a risk factor for CHD (9). LPL can be synthesized in skeletal muscle; in adipose, heart, lung, and brain tissue; and in macrophages (10). Its physiological location, however, is on the luminal surface of the capillary endothelium (11).

The human LPL gene is located on chromosome 8p22 (12), and its gene structure and cDNA have been described (13)(14)(15)(16)(17). Several restriction fragment length polymorphisms in the LPL gene have been documented and associated with various lipid traits (18)(19)(20)(21). This study focused on the LPL HindIII polymorphism in which a replacement of a thymine (T) with a guanine (G) base occurs at position +495 in intron 8 and abolishes a HindIII restriction enzyme recognition site (22). It has been hypothesized that the more common H+ allele (presence of cutting site) is associated with a lower LPL activity compared with the rare H- allele (absence of the restriction site). As such, it has been proposed that carriers with the H+/+ genotype have higher triglyceride concentrations and lower HDL concentrations vs carriers of the H-/- genotype.

Although in some studies the common H+ allele of the LPL HindIII polymorphism has been shown to be significantly associated with hypertriglyceridemia (23)(24)(25)(26)(27)(28), hypercholesterolemia (9), lower HDL (9)(29)(30), increased apolipoprotein C-III (30) and apolipoprotein B (27), and premature CHD (24)(27)(29)(30), other reports failed to note such effects (23)(31)(32)(33). The inconsistency of those reports may be attributable to small sample sizes or heterogeneity with regard to the ethnic backgrounds, ages, and sexes of study subjects. More importantly, differences in diet and lifestyle may have been responsible for this disparity. Previous studies failed to account for dietary influences that have been reported to have an effect on LPL activity (34)(35).

Therefore, the aims of this study were (a) to reduce the variability of various lipoprotein phenotypes by stabilizing study subjects with the help of a dietary and lifestyle intervention program before analysis; (b) to investigate associations between the LPL HindIII genotypes and several lipid traits in a large study population; and (c) to identify the gene-gender difference of this polymorphism regarding lipid and lipoprotein concentrations.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
subjects
A total of 683 middle-aged and elderly subjects participated in this study. All study subjects (342 females and 341 males) took part in a lifestyle intervention program at a residential center in California, which included a low-fat/low-cholesterol, but high-complex carbohydrate/high-fiber diet. Furthermore, people participated in a daily exercise program that included 30–40 min of walking and 60 min of supervised fitness classes. This program previously has been described in detail (36). Fasting blood samples were drawn after a period of 8 days. Some data suggest that this diet period in combination with physical activity produces sufficient normalization of plasma lipid concentrations (37)(38). Information on the study subjects is provided in Table 1 . The menopausal status of women was not assessed.


View this table:
[in this window]
[in a new window]
  		Table 1. Study subjects.

blood sampling
All subjects were sampled after an 8-day intervention period and an overnight fast of at least 12 h. Blood samples were placed in SST clot-activating gel tubes (Becton-Dickinson Vacutainer System) or in two 10-mL EDTA tubes (1 g/L EDTA) for the isolation of DNA. Serum was used for the determination of serum lipids and glucose. Non-HDL lipoproteins were precipitated using the sodium phosphotungstic acid reagent. The total cholesterol, HDL-cholesterol, triglyceride, and glucose concentrations were measured using standard automated enzymatic procedures on an Olympus automated analyzer (Smith-Kline Beecham Laboratories). LDL-cholesterol was calculated by subtracting the sum of the HDL-cholesterol and triglycerides divided by 5 from total cholesterol, as described by Friedewald et al. (39), provided triglyceride concentrations were <4.52 mmol/L (400 mg/dL).

genotyping
Genomic DNA was isolated from whole blood, using the QIAamp Blood Kit (Qiagen). The HindIII genotype in intron 8 of the LPL gene was determined by PCR followed by digestion with the restriction endonuclease HindIII and agarose gel electrophoresis as described previously (27). The resulting restriction fragment length polymorphism fragments were 356 bp (uncut) for the H- allele or 217 and 139 bp (cut) for the H+ allele. In 180 randomly selected individuals, the S447X mutation of LPL was also assessed as described (40).

statistical analysis
Statistical analysis was performed with the software package SPSS/PC+. The statistical significance was set at {alpha} = 0.05. Allele frequencies for the HindIII polymorphic site were estimated by gene counting. Agreement of the genotype frequencies with the Hardy-Weinberg equilibrium expectations was tested using a {chi}2 goodness-of-fit test. All variables were tested for gaussian distribution. Data for body mass index (BMI), plasma glucose, HDL, and triglycerides were log10 transformed before analysis of covariance to reduce the skewness of the data. The antilogs and unadjusted mean values ± SD of the lipid traits are presented in Tables 2 and 3. Analyses were performed separately in females and males. Comparisons of the glucose, lipid, and lipoprotein traits between females and males were performed with the Student t-test.

Covariance adjustments were made for age, BMI, smoking status, alcohol use, and medications (cholesterol-lowering drugs, diabetes medication, hormonal replacements, and thyroid supplementation). Analysis of covariance was performed to test the null hypothesis that phenotypic variations in these traits were not associated with genetic variation at the candidate gene locus. The continuous variables (age and BMI) were entered in the general linear model as covariates. The dichotomous variables (smoking status, alcohol use, and medications) were included as factors. In cases involving significant effects of genetic variability on lipid traits, one-way ANOVA (Tukey test) was performed to compare interindividual differences between genotypes.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The data on the biochemical variables for females and males are listed in Table 2 . Males had higher concentrations of fasting plasma glucose and triglycerides and lower total cholesterol and HDL-cholesterol compared with females. For LDL-cholesterol, no gender difference was observed. For both women and men, the genotype distributions were in accordance with the Hardy-Weinberg expectation. The rarer H- allele occurred at a frequency of 0.29 in women and 0.34 in men. The common H+ allele occurred at a frequency of 0.71 in women and 0.66 in men (Table 3 ). These data indicated no statistical significant difference between females and males with regard to HindIII genotype distribution. Investigation of the HindIII polymorphism and the LPL S447X variant revealed in a random subset of 180 subjects (data not shown) a significant linkage disequilibrium between these two polymorphisms, as described previously (40).


View this table:
[in this window]
[in a new window]
  		Table 2. Biochemical variables.


View this table:
[in this window]
[in a new window]
  		Table 3. LPL HindIII genotype frequencies.

The data on the biochemical variables by gender and LPL HindIII genotype are listed in Table 4 . With regard to total cholesterol, females showed a significant association (P = 0.007) between the HindIII genotypes and total cholesterol: Women homozygous for the H- allele had the lowest total-cholesterol concentrations, those being heterozygous had intermediate concentrations, and women carrying both H+ alleles had the highest concentrations. The same gene-dosage effect was also observed in women with regard to LDL-cholesterol. Whereas women having the H-/- genotype had the lowest LDL concentrations, at 2.55 mmol/L, those having the H+/+ genotype had the highest concentrations, at 2.98 mmol/L (P = 0.018). The same trend, although not statistically significant, was noted if women on hormone replacement therapy were tested separately (data not shown). In the male population, no significant difference between the HindIII genotype and total cholesterol or LDL-cholesterol was found. HDL-cholesterol and triglyceride concentrations showed no difference in either gender.


View this table:
[in this window]
[in a new window]
  		Table 4. Biochemical variables and HindIII polymorphisms.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
LPL is known to be the rate-limiting enzyme in triglyceride catabolism. Knowing that environmental factors such as diet and lifestyle can significantly influence the lipid and lipoprotein concentrations, we took a new approach and reduced the variability of those factors on lipid traits by placing all study subjects on a low-fat, low-cholesterol diet, exercise, and lifestyle modification program before analysis. By recruiting a large number of people, we could study a possible gene-gender interaction.

The genotype distribution of the HindIII polymorphism in this study was not significantly different from the Hardy-Weinberg equilibrium, and the overall allele frequencies were similar to previously published studies in Caucasians (9)(23)(24)(29)(30)(32)(33).

In females, the H+ allele was associated with higher concentrations of total cholesterol and LDL-cholesterol. There was a clear gene-dosage effect in females, with H+ homozygotes having the highest cholesterol concentrations, heterozygotes having intermediate concentrations, and H- homozygotes having the lowest concentrations. In males, however, no effect was observed for total and LDL-cholesterol. The majority of previous studies did not find significant associations between the LPL HindIII genotype and total or LDL-cholesterol. Mattu et al. (27), however, also reported an association between the HindIII H+ allele and total and LDL-cholesterol as well as the gene-dosage effect, with H+ subjects having the highest and H- subjects having the lowest lipid concentrations.

Our results may now provide an explanation for previously reported associations of the H+ allele and CHD (24)(27)(41)(42). Thorn et al. (24) reported in Caucasians with severe coronary artery disease a significantly higher frequency of the H+ allele compared with healthy controls. Furthermore, Chen et al. (41) not only indicated that individuals with the H+/+ genotype had a significantly higher mean carotid wall thickness, but that the H+/+ genotype was also associated with hypertriglyceridemia and hypercholesterolemia. Patients with type 2 diabetes mellitus and the H+/+ genotype were reported to have the highest prevalence of CHD (90%) compared with the H-/+ (55.4%) and H-/- (54.6%) genotypes, respectively (43).

It is believed that the HindIII polymorphism is in linkage disequilibrium with one or more regions within or in close proximity to the LPL gene, affecting LPL activity and/or the clearance rate of triglyceride-rich lipoproteins and their remnants. In fact, a recent report by Humphries et al. (40) provides strong evidence for significant linkage disequilibrium between the HindIII site and the LPL S447X mutation. Recently, it has been shown that the S447X mutation is associated with increased LPL activity (44). Therefore, individuals with the HindIII site and the LPL wild type would be expected to have lower LPL activity. Our results can also be compared with patients who are heterozygous for familial LPL deficiency and are characterized by LPL activity reduced by 50%. Brunzell (45) and Miesenboeck et al. (46) detected in some of these patients abnormalities across the lipoprotein density spectrum, including an increase in VLDL or intermediate-density lipoproteins and small, dense LDL particles. Furthermore, this alteration in lipoprotein composition might cause a reduced affinity of those particles to the LDL receptor, which could explain the higher LDL concentrations. In addition, nonenzymatic effects of LPL, such as its bridging function, may be more efficient in individuals with the S447 stop mutation (40).

We could not demonstrate a significant association between the HindIII genotype and HDL-cholesterol or triglycerides in either females or males. Assuming that the polymorphism is associated with the LPL activity, one would expect to find lower HDL-cholesterol and higher triglyceride concentrations in carriers with the H+ allele. Humphries et al. (40), who studied the effects of the H- X447 haplotype on triglyceride concentrations, demonstrated that the impact, although significant, was small. Hence, our findings do not rule out an association between the HindIII polymorphism and LPL activity. It is also conceivable that LPL activity in individuals with the H+ allele was still high enough for effective triglyceride hydrolysis; however, LPL activity was already too low to facilitate efficient uptake of remnants, leading to increased LDL concentrations (47)(48). Affected individuals may exhibit increased triglyceride concentrations only after an alimentary triglyceride load or lack of physical activity.

In terms of the gene-gender effect, a difference with regard to the LPL HindIII polymorphism and various lipid traits was noted. At present, we can only speculate about the underlying mechanism. The metabolic reason for this gene-gender difference might be related to hormones, but further investigation is needed before a hypothesis can be put forward.


   Footnotes
 
1 Nonstandard abbreviations: LPL, lipoprotein lipase; CHD, coronary heart disease; and BMI, body mass index.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Goldberg IJ. Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. J Lipid Res 1996;37:693-707. [Abstract]
  2. Jackson RL. Lipoprotein lipase and hepatic lipase. Boyer P eds. The enzymes 1983;Vol. 16:141-181 Academic Press New York. .
  3. Garfinkel AS. Lipoprotein lipase. Gotto AM eds. Plasma lipoproteins 1987:335-357 Elsevier New York. .
  4. Beisiegel U, Weber W, Bengtsson-Olivecrona G. Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein. Proc Natl Acad Sci U S A 1991;88:8342-8346. [Abstract/Free Full Text]
  5. Patsch JR, Prasad S, Gotto AM, Patsch W. High density lipoprotein. 2. Relationship of the plasma levels of this lipoprotein species to its composition, to the magnitude of postprandial lipemia, and to the activities of lipoprotein lipase and hepatic lipase. J Clin Investig 1987;80:341-347.
  6. Miller NE. HDL cholesterol, tissue cholesterol, and coronary atherosclerosis: epidemiological correlations. Gotto AM, Jr Allen B eds. Atherosclerosis 1980:500-503 Springer New York. .
  7. Breslow JL. Genetic basis of lipoprotein disorders. J Clin Investig 1989;84:373-380.
  8. Lusis AJ. Genetic factors affecting blood lipoproteins: the candidate gene approach. J Lipid Res 1988;29:397-430. [ISI][Medline] [Order article via Infotrieve]
  9. Heinzmann C, Kirchgessner T, Kwiterovich PO, Ladias JA, Derby C, Antonarakis SE, et al. DNA polymorphism haplotypes of the human lipoprotein lipase gene: possible association with high density lipoprotein levels. Hum Genet 1991;86:578-584. [ISI][Medline] [Order article via Infotrieve]
  10. Enerbaeck S, Gimble JM. Lipoprotein lipase gene expression: physiological regulators at the transcriptional and post-transcriptional level. Biochim Biophys Acta 1993;1169:107-125. [Medline] [Order article via Infotrieve]
  11. Quinn D, Shira K, Jackson RL. Lipoprotein lipase: mechanism of action and role in lipoprotein metabolism. Prog Lipid Res 1982;22:35-78.
  12. Sparkes RS, Zollman S, Klisak I, Kirchgessner TD, Komaromy M, Mohandas T, et al. Human genes involved in lipolysis of plasma lipoproteins: mapping of loci for lipoprotein lipase to 8p22 and hepatic lipase to 15q21. Genomics 1987;1:138-144. [Medline] [Order article via Infotrieve]
  13. Wion KL, Kirchgessner TG, Lusis AJ, Schotz MC, Lawn RM. Human lipoprotein lipase complementary DNA sequence. Science 1987;235:1638-1641. [Abstract/Free Full Text]
  14. Deeb SS, Peng R. Structure of the human lipoprotein lipase gene. Biochemistry 1989;28:4131-4135. [Medline] [Order article via Infotrieve]
  15. Kirchgessner TD, Chuat JC, Heinzmann C, Etienne J, Guilhot S, Svenson K, et al. Organization of the human lipoprotein lipase gene and evolution of the lipase gene family. Proc Natl Acad Sci U S A 1989;86:9647-9651. [Abstract/Free Full Text]
  16. Oka K, Tkalcevic GT, Nakano T, Tucker H, Ishimura-Oka K, Brown WV. Structure and polymorphic map of human lipoprotein lipase gene. Biochim Biophys Acta 1990;1049:21-26. [Medline] [Order article via Infotrieve]
  17. Chuat J-C, Raisonnier A, Etienne J, Galibert F. The lipoprotein lipase-encoding human gene: sequence from intron-6 to intron-9 and presence in intron-7 of a 40-million-year-old Alu sequence. Gene 1992;110:257-261. [ISI][Medline] [Order article via Infotrieve]
  18. Fischer KL, FitzGerald GA, Lawn RM. Two polymorphisms in the human lipoprotein lipase (LPL) gene. Nucleic Acid Res 1987;15:7657.[Free Full Text]
  19. Heinzmann C, Ladias J, Antonarakis S, Kirchgessner T, Schotz M, Lusis AJ. RFLP for the human lipoprotein lipase (LPL) gene; HindIII. Nucleic Acids Res 1987;15:6763.[Free Full Text]
  20. Li S, Oka K, Galton D, Stocks J. Pvu-II RFLP at the human lipoprotein lipase (LPL) gene. Nucleic Acids Res 1988;16:2358.[Free Full Text]
  21. Hata A, Robertson M, Emi M, Lalouel JM. Direct detection and automated sequencing of individual alleles after electrophoretic strand separation: identification of a common nonsense mutation in exon 9 of the human lipoprotein lipase gene. Nucleic Acids Res 1990;18:5407-5411. [Abstract/Free Full Text]
  22. Gotoda T, Yamada N, Murase T, Shimano H, Shimada M, Harada K, et al. Detection of three separate DNA polymorphisms in the human lipoprotein lipase gene by gene amplification and restriction endonuclease digestion. J Lipid Res 1992;33:1067-1072. [Abstract]
  23. Chamberlain JC, Thorn JA, Oka K, Galton DJ, Stocks J. DNA polymorphisms at the lipoprotein lipase gene: associations in normal and hypertriglyceridemic subjects. Atherosclerosis 1989;79:85-91. [ISI][Medline] [Order article via Infotrieve]
  24. Thorn JA, Chamberlain JC, Alcolando JC, Oka K, Chan L, Stocks J, et al. Lipoprotein and hepatic lipase gene variants in coronary atherosclerosis. Atherosclerosis 1990;85:55-60. [ISI][Medline] [Order article via Infotrieve]
  25. Peacock RE, Hamsten A, Nilsson-Ehle P, Humphries SE. Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden. Atherosclerosis 1992;97:171-185. [ISI][Medline] [Order article via Infotrieve]
  26. Ahn YI, Kamboh MI, Hamman RF, Cole SA, Ferrel RE. Two DNA polymorphisms in the lipoprotein lipase gene and their associations with factors related to cardiovascular disease. J Lipid Res 1993;34:421-428. [Abstract]
  27. Mattu RK, Needham EWA, Morgan R, Rees A, Hackshaw AK, Stocks J, et al. DNA variants at the LPL gene locus associate with angiographically defined severity of atherosclerosis and serum lipoprotein levels in a Welsh population. Arterioscler Thromb 1994;14:1090-1097. [Abstract/Free Full Text]
  28. Jemaa R, Tuzet S, Portos C, Betoulle D, Apfelbaum M, Fumeron F. Lipoprotein lipase gene polymorphisms: associations with hypertriglyceridemia and body mass index in obese people. Int J Obes 1995;19:270-274.
  29. Gerdes C, Gerdes LU, Hansen PS, Faergeman O. Polymorphisms in the lipoprotein lipase gene and their associations with plasma lipid concentrations in 40-year-old Danish men. Circulation 1995;92:1765-1769. [Abstract/Free Full Text]
  30. Jemaa R, Fumeron F, Poirier O, Lecerf L, Evans A, Arveiler D, et al. Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels, the ECTIM study. J Lipid Res 1995;36:2141-2146. [Abstract]
  31. Vohl MC, Lamarche B, Moorjani S, Prud'homme D, Nadeau A, Bouchard C, et al. The lipoprotein lipase HindIII polymorphism modulates plasma triglyceride levels in visceral obesity. Arterioscler Thromb Vasc Biol 1995;15:714-720. [Abstract/Free Full Text]
  32. Georges JL, Regis-Bailly A, Salah D, Rakotovao R, Siest G, Visvikis S, et al. Family study of lipoprotein lipase gene polymorphisms and plasma triglyceride levels. Genet Epidemiol 1996;13:179-192. [ISI][Medline] [Order article via Infotrieve]
  33. Peacock RE, Temple A, Gudnason V, Rosseneu M, Humphries S. Variation at the lipoprotein lipase and apolipoprotein AI-CIII gene loci are associated with fasting lipid and lipoprotein traits in a population sample from Iceland: interaction between genotype, gender, and smoking status. Genet Epidemiol 1997;14:265-282. [ISI][Medline] [Order article via Infotrieve]
  34. Ong JM, Kern PA. Effect of feeding and obesity on lipoprotein lipase activity, immunoreactive protein, and messenger RNA levels in human adipose tissue. J Clin Investig 1989;84:305-311.
  35. Olivecrona T, Bergo M, Hultin M, Olivecrona G. Nutritional regulation of lipoprotein lipase. Can J Cardiol 1995;11:73G-78G.
  36. Barnard RJ. Effects of life-style modification on serum lipids. Arch Intern Med 1991;151:1389-1394. [Abstract]
  37. Oscai LB, Patterson JA, Bogard DL, Beck RJ, Rothermel BL. Normalization of serum triglycerides and lipoprotein electrophoretic patterns by exercise. Am J Cardiol 1972;30:775-780. [ISI][Medline] [Order article via Infotrieve]
  38. Barnard RJ, Pritikin N. Approach to cardiac rehabilitation. Goodgold J eds. Rehabilitation medicine 1988:267-284 CV Mosby St. Louis, MO. .
  39. Friedewald WT, Levy RI, Frerickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502. [Abstract]
  40. Humphries SE, Nicaud V, Margalef J, Tiret L, Talmud PJ. Lipoprotein lipase gene variation is associated with a paternal history of premature coronary artery disease and fasting and postprandial plasma triglycerides: the European Atherosclerosis Research Study (EARS). Arterioscler Thromb Vasc Biol 1998;18:526-534. [Abstract/Free Full Text]
  41. Chen L, Patsch W, Boerwinkle E. HindIII DNA polymorphism in the lipoprotein lipase gene and plasma lipid phenotypes and carotid artery atherosclerosis. Hum Genet 1996;98:551-556. [ISI][Medline] [Order article via Infotrieve]
  42. Wang XL, McCredie RM, Wilken DEL. Common DNA polymorphisms at the lipoprotein lipase gene. Association with severity of coronary artery disease and diabetes. Circulation 1996;93:1339-1345. [Abstract/Free Full Text]
  43. Ukkola O, Savolainen MJ, Salmela PI, von Dickhoff K, Kesaniemi YA. DNA polymorphisms at the lipoprotein lipase gene are associated with macroangiopathy in type 2 (non-insulin-dependent) diabetes mellitus. Atherosclerosis 1995;115:99-105. [ISI][Medline] [Order article via Infotrieve]
  44. Zhang H, Henderson H, Gagne SE, Clee SM, Miao L, Liu G, et al. Common sequence variants of lipoprotein lipase: standardized studies of in vitro expression and catalytic function. Biochim Biophys Acta 1996;1302:159-166. [Medline] [Order article via Infotrieve]
  45. Brunzell JD. Familial lipoprotein lipase deficiency and other causes of the chylomicronemia syndrome. Scriver CR Beaudet AL Sly WS Valle D eds. The metabolic and molecular basis of inherited disease 7th ed. 1995:1913-1932 McGraw-Hill New York. .
  46. Miesenboeck G, Hoelzl B, Foger B, Brandstaetter E, Paulweber B, Sandhofer F, et al. Heterozygous lipoprotein lipase deficiency due to a missense mutation as the cause of impaired triglyceride tolerance with multiple lipoprotein abnormalities. J Clin Investig 1993;91:448-455.
  47. Demant T, Gaw A, Watts GF, Durrington P, Buckley P, Imrie CW, et al. Metabolism of apoB-100-containing lipoproteins in familial hyperchylomicronemia. J Lipid Res 1993;34:147-156. [Abstract]
  48. Packard CJ, Shepherd J. Lipoprotein heterogeneity and apolipoprotein B metabolism. Arteriosclerosis Thromb Vasc Biol 1997;17:3542-3556. [Abstract/Free Full Text]



The following articles in journals at HighWire Press have cited this article:


Home page
 Am J EpidemiolHome page
G. S. Sagoo, I. Tatt, G. Salanti, A. S. Butterworth, N. Sarwar, M. van Maarle, J. W. Jukema, B. Wiman, J. J. P. Kastelein, A. M. Bennet, et al.
Seven Lipoprotein Lipase Gene Polymorphisms, Lipid Fractions, and Coronary Disease: A HuGE Association Review and Meta-Analysis
Am. J. Epidemiol., December 1, 2008; 168(11): 1233 - 1246.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
D. Corella, M. Guillen, C. Saiz, O. Portoles, A. Sabater, J. Folch, and J. M. Ordovas
Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a Mediterranean population: interaction with tobacco smoking and the APOE locus
J. Lipid Res., March 1, 2002; 43(3): 416 - 427.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (13)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Larson, I.
Right arrow Articles by Kreuzer, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Larson, I.
Right arrow Articles by Kreuzer, J.
Related Collections
Right arrow Molecular Diagnostics and Genetics
Right arrow Lipids, Lipoproteins, and Cardiovascular Risk Factors

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS