title: Gene variants of VAMP8 and HNRPUL1 are associated with early-onset myocardial infarction.
abstract: OBJECTIVE
  Identify gene variants associated with early-onset myocardial infarction (MI).
  
  
  RESULTS
  We tested 11 647 single-nucleotide polymorphisms (SNPs) for association with early-onset MI in a case-control study (study 1 200 cases, 262 controls). To reduce the number of false positives among the 666 SNPs that were nominally associated with early-onset MI (P<0.05) in study 1, we tested these SNPs in study 2 (434 cases, 504 controls). We found that 8 of the 666 SNPs were associated with early-onset MI in study 2 (P<0.05) and had the same risk alleles as in study 1. These 8 SNPs were then tested for association with early-onset MI in study 3 (187 cases, 434 controls). We found that a VAMP8 variant (P = 0.025; odds ratio [OR], 1.75; CI, 1.17 to 2.62) and an HNRPUL1 variant (P = 0.0043; OR, 1.92; CI, 1.28 to 2.86) were associated with early-onset MI (nominal P<0.05; false discovery rate <10%) and had the same risk alleles in all 3 studies.
  
  
  CONCLUSIONS
  Variants in 2 genes were associated with early-onset MI: VAMP8, which is involved in platelet degranulation, and HNRPUL1, which encodes a ribonuclear protein. The identification of these variants could improve understanding of disease mechanisms and suggest novel drug targets.
authors.affiliation: Celera Inc., 1401 Harbor Bay Pkwy, Alameda, California 94502, USA. dov.shiffman@celeradiagnostics.com
authors.forename: Dov
authors.initials: D
authors.lastname: Shiffman
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rowland
authors.forename: Judy Z
authors.initials: JZ
authors.lastname: Louie
authors.forename: May M
authors.initials: MM
authors.lastname: Luke
authors.forename: Lance A
authors.initials: LA
authors.lastname: Bare
authors.forename: Joel I
authors.initials: JI
authors.lastname: Bolonick
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Young
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Catanese
authors.forename: Charles F
authors.initials: CF
authors.lastname: Stiggins
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Malloy
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ellis
authors.forename: James J
authors.initials: JJ
authors.lastname: Devlin
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D050683:R-SNARE Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C475078:HNRNPUL1 protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D050683:R-SNARE Proteins; D014157:Transcription Factors; C112938:VAMP8 protein, human