title: SREBP-2 and SCAP isoforms and risk of early onset myocardial infarction.
abstract: BACKGROUND
  Cholesterol metabolism is mediated, in part, by the sterol-regulatory element binding proteins (SREBPs) that are activated by a SREBP cleavage-activating protein (SCAP). We examined whether coding variations in the interacting domains of both genes, are related to early-onset MI risk in a population-based case-control study from western Washington State.
  
  
  METHODS
  Cases were 257 women, aged 18-59 years, and 320 men, aged 18-49 years, with first acute non-fatal MI; controls were 353 women and 311 men, similar in age, identified from the community who had no history of clinical CHD or stroke. Genotyping of the SREBF-2 G1784C polymorphism (SREBP-2-595A/G isoforms), and the SCAP A2386G polymorphism (SCAP-796I/V isoforms), were performed.
  
  
  RESULTS
  After adjustment for age and race, the SREBP-2-595A isoform was associated with increased MI risk among men (OR=1.63, 95% CI=1.26-2.12). In contrast, there was little evidence for an association among women in a multiplicative model. However, compared to SREBP-2-595G homozygotes, homozygote women for the SREBP-2-595A isoform were at nearly two-fold increased risk (OR=1.95, 95% CI=1.07-3.54). Overall, SCAP genotypes were neither associated with MI in men nor in women. However, in men, SCAP genotypes were found to modify the association between SREBF-2 and MI (p-value for interaction=0.01).
  
  
  CONCLUSIONS
  The SREBP-2-595A isoform was associated with an increased risk of early-onset MI in U.S. men. The SCAP polymorphism appeared to modify the associations of SREBF-2 genotype with MI risk among men. These novel findings require confirmation in other populations.
authors: Unit of Epidemiology, Hebrew University-Hadassah School of Public Health, Jerusalem, Israel.
authors: Yechiel
authors: Y
authors: Friedlander
authors: Stephen M
authors: SM
authors: Schwartz
authors: Ronen
authors: R
authors: Durst
authors: Vardiella
authors: V
authors: Meiner
authors: Andrea S
authors: AS
authors: Robertson
authors: Gilli
authors: G
authors: Erez
authors: Eran
authors: E
authors: Leitersdorf
authors: David S
authors: DS
authors: Siscovick
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics; D012306:Risk; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; C497390:SREBF2 protein, human; C102196:SREBP cleavage-activating protein; D051782:Sterol Regulatory Element Binding Protein 2