Association of genetic variants in SEMA3F, CLEC16A, LAMA3, and PCSK2 with myocardial infarction in Japanese individuals.
OBJECTIVE
The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in Japanese individuals.


METHODS
The study population comprised 5014 Japanese individuals, including 1444 subjects with MI and 3570 controls. The 150 polymorphisms examined in the present study were selected by a genome-wide association study for ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix), and were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.


RESULTS
An initial screen by the chi-square test revealed that the A-->G polymorphism of SEMA3F (rs12632110), the C-->T polymorphism of CLEC16A (rs9925481), the A-->G polymorphism of LAMA3 (rs12373237), and the C-->G polymorphism of PCSK2 (rs6080699) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure revealed that the A-->G polymorphism of SEMA3F (dominant model; P=0.0014; odds ratio, 0.76), the C-->T polymorphism of CLEC16A (dominant model; P=0.0009; odds ratio, 0.75), the A-->G polymorphism of LAMA3 (recessive model; P=0.0099; odds ratio, 0.80), and the C-->G polymorphism of PCSK2 (recessive model; P=0.0155; odds ratio, 1.19) were significantly (P<0.05) associated with the prevalence of MI.


CONCLUSIONS
Determination of these genotypes may prove informative for assessment of the genetic risk for MI in Japanese individuals.
Fujimaki
Tetsuo
T
Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.
Kato
Kimihiko
K
Yokoi
Kiyoshi
K
Oguri
Mitsutoshi
M
Yoshida
Tetsuro
T
Watanabe
Sachiro
S
Metoki
Norifumi
N
Yoshida
Hidemi
H
Satoh
Kei
K
Aoyagi
Yukitoshi
Y
Nozawa
Yoshinori
Y
Kimura
Genjiro
G
Yamada
Yoshiji
Y
D000368:Aged; D050197:Atherosclerosis / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D007564:Japan; D007797:Laminin / Q000235:genetics*; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D045706:Proprotein Convertase 2 / Q000235:genetics*
C522505:CLEC16A protein, human; D007797:Laminin; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; C491230:SEMA3F protein, human; C095567:laminin alpha 3; D045706:Proprotein Convertase 2