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Lipoprotein Lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS

Alexis C Wood12*, Stephen Glasser3, W Timothy Garvey4, Edmond K Kabagambe15, Ingrid B Borecki6, Hemant K Tiwari2, Michael Y Tsai7, Paul N Hopkins8, Jose M Ordovas109 and Donna K Arnett15

Author Affiliations

1 Department of Epidemiology, University of Alabama at Birmingham, School of Public Health, Alabama, USA

2 Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, School of Public Health, Alabama, USA

3 Department of Medicine, Division of Preventive Medicine, University of Alabama at Birmingham, Alabama, USA

4 Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA

5 Nutrition Obesity Research Center, University of Alabama at Birmingham, School of Public Health, Alabama, USA

6 Division of Statistical Genomics, Department of Genetics, Washington University, School of Medicine, 4444 Forest Park Boulevard - Box 8506, St. Louis, Missouri, USA

7 Department of Laboratory Medicine and Pathology, University of Minnesota, MN, USA

8 Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA

9 Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA

10 The Department of Epidemiology and Population Genetics. Centro Nacional Investigación Cardiovasculares Madrid, Spain

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Lipids in Health and Disease 2011, 10:143  doi:10.1186/1476-511X-10-143

Published: 19 August 2011

Abstract

Background

Previous analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified groups (N = 251), ~75% of individuals met Adult Treatment Panel III criteria for the metabolic syndrome (MetS). Both showed small LDL diameter (mean = 19.9 nm); however, group 1 (N = 200) had medium VLDL diameter (mean = 53.1 nm) while group 2 had very large VLDL diameter (mean = 65.74 nm). Group 2 additionally showed significantly more insulin resistance (IR), and accompanying higher waist circumference and fasting glucose and triglycerides (all P < .01). Since lipoprotein lipase hydrolyzes triglyceride in the VLDL-LDL cascade, we examined whether these two patterns of lipoprotein diameter were associated with differences across two lipoprotein lipase (LPL) gene variants: D9N (rs1801177) and S447X (rs328).

Findings

Mixed linear models that controlled for age, sex, center of data collection, and family pedigree revealed no differences between the two groups for the D9N polymorphism (P = .36). However, group 2 contained significantly more carriers (25%) of the 447X variant than group 1 (14%; P = .04).

Conclusions

This was the first study this kind to show an association between LPL and large VLDL particle size within the MetS, a pattern associated with higher IR. Future work should extend this to larger samples to confirm these findings, and examine the long term outcomes of those with this lipoprotein diameter pattern.

Keywords:
GOLDN; lipoprotein; lipoprotein lipase; Metabolic syndrome