Gene variants of VAMP8 and HNRPUL1 are associated with early-onset myocardial infarction.
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.
Shiffman
Dov
D
Celera Inc., 1401 Harbor Bay Pkwy, Alameda, California 94502, USA. dov.shiffman@celeradiagnostics.com
Rowland
Charles M
CM
Louie
Judy Z
JZ
Luke
May M
MM
Bare
Lance A
LA
Bolonick
Joel I
JI
Young
Bradford A
BA
Catanese
Joseph J
JJ
Stiggins
Charles F
CF
Pullinger
Clive R
CR
Topol
Eric J
EJ
Malloy
Mary J
MJ
Kane
John P
JP
Ellis
Stephen G
SG
Devlin
James J
JJ
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*
C475078:HNRNPUL1 protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D050683:R-SNARE Proteins; D014157:Transcription Factors; C112938:VAMP8 protein, human