title: Haplotypes in the lipoprotein lipase gene influence fasting insulin and discovery of a new risk haplotype.
abstract: BACKGROUND
  Prior studies of Mexican Americans described association of lipoprotein lipase (LPL) gene haplotypes with insulin sensitivity/resistance and atherosclerosis. The most common haplotype (haplotype 1) was protective, whereas the fourth most common haplotype (haplotype 4) conferred risk for insulin resistance and atherosclerosis.
  
  
  OBJECTIVE
  In this study of Hispanics in the Insulin Resistance Atherosclerosis Study Family Study, we sought to replicate LPL haplotype association with insulin sensitivity/resistance.
  
  
  METHODS
  LPL haplotypes based on 12 single nucleotide polymorphisms were analyzed for association with indexes of insulin sensitivity and other metabolic and adiposity measures.
  
  
  METHODS
  This study was conducted in the general community of San Antonio, Texas, and San Luis Valley, Colorado.
  
  
  METHODS
  Participants in this study were 978 members of 86 Hispanic families.
  
  
  METHODS
  LPL haplogenotype, metabolic phenotypes, and adiposity were measured in this study.
  
  
  RESULTS
  The haplotype structure was identical with that observed in prior studies. Among 978 phenotyped subjects, haplotype 1 was associated with decreased fasting insulin (P = 0.01), and haplotype 4 was associated with increased fasting insulin (P = 0.02) and increased visceral fat mass (P = 0.002). Insulin sensitivity, derived from iv glucose tolerance testing, tended (P > 0.1) to be higher with haplotype 1 (S(I) = 1.72) and lower with haplotype 4 (S(I)=1.38). Haplotype 2 was associated with increases in fasting insulin, triglycerides (TGs), TG to high-density lipoprotein-cholesterol ratio, and apolipoprotein B (P = 0.01-0.04).
  
  
  CONCLUSIONS
  This study independently replicates our prior results of LPL haplotypes 1 and 4 as associated with measures of insulin sensitivity and resistance, respectively. Haplotype 4 may confer insulin resistance by increasing visceral fat. Haplotype 2 was identified as a new risk haplotype, suggesting the complex nature of LPL's effect on features of the insulin resistance syndrome.
authors.affiliation: Cedars-Sinai Medical Center, Division of Endocrinology, Diabetes, and Metabolism, 8700 Beverly Boulevard, Becker B-131, Los Angeles, California 90048, USA. mark.goodarzi@cshs.org
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Steven M
authors.initials: SM
authors.lastname: Haffner
authors.forename: Jinrui
authors.initials: J
authors.lastname: Cui
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
mesh_terms: D005215:Fasting / Q000097:blood*; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008071:Lipoprotein Lipase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D007328:Insulin; D008071:Lipoprotein Lipase