title: Lipoprotein lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS.
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).
  
  
  RESULTS
  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.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, School of Public Health, Alabama, USA. LekkiWood@Gmail.com
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Wood
authors.forename: Stephen
authors.initials: S
authors.lastname: Glasser
authors.forename: W Timothy
authors.initials: WT
authors.lastname: Garvey
authors.forename: Edmond K
authors.initials: EK
authors.lastname: Kabagambe
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D016000:Cluster Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007333:Insulin Resistance; D008071:Lipoprotein Lipase / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000737:chemistry*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D010316:Particle Size; D010375:Pedigree; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014481:United States
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C548261:LPL protein, human; D008071:Lipoprotein Lipase