Association of genetic variants with myocardial infarction in Japanese individuals with metabolic syndrome.
OBJECTIVE
The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in individuals with metabolic syndrome (MetS).


METHODS
The study population comprised 1887 Japanese individuals with MetS, including 773 subjects with MI and 1114 controls. The genotypes for 136 polymorphisms of 97 candidate genes were determined.


RESULTS
An initial screen by the chi-square test revealed that seven polymorphisms were significantly (false discovery rate<0.05) associated with the prevalence of MI in individuals with MetS. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the G-->A (Ser89Asn) polymorphism of UTS2 [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.18-3.08], the 2445G-->A (Ala54Thr) polymorphism of FABP2 (OR, 1.72; 95% CI, 1.23-2.40), the -11377C-->G polymorphism of ADIPOQ (OR, 1.43; 95% CI, 1.15-1.79), the -231A-->G polymorphism of EDNRA (OR, 0.65; 95% CI, 0.48-0.89), and the -108/3G-->4G polymorphism of PDX1 (OR, 0.64; 95% CI, 0.48-0.87) were significantly (P<0.05) associated with MI. The variant alleles of UTS2, FABP2, and ADIPOQ were risk factors for MI, whereas the variant alleles of EDNRA and PDX1 were protective against this condition. A stepwise forward selection procedure demonstrated that UTS2, FABP2, ADIPOQ, EDNRA, and PDX1 genotypes were significant (P<0.05) and independent determinants of MI.


CONCLUSIONS
Determination of genotypes for these polymorphisms of UTS2, FABP2, ADIPOQ, EDNRA, and PDX1 may prove informative for assessment of the genetic risk for MI in Japanese individuals with MetS.
Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
Mitsutoshi
M
Oguri
Kimihiko
K
Kato
Kiyoshi
K
Yokoi
Tatsuo
T
Itoh
Tetsuro
T
Yoshida
Sachiro
S
Watanabe
Norifumi
N
Metoki
Hidemi
H
Yoshida
Kei
K
Satoh
Yukitoshi
Y
Aoyagi
Yutaka
Y
Nishigaki
Masashi
M
Tanaka
Yoshinori
Y
Nozawa
Yoshiji
Y
Yamada
D052242:Adiponectin / Q000235:genetics; D000368:Aged; D044466:Asian People / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017466:Receptors, Endothelin / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014579:Urotensins / Q000235:genetics
D052242:Adiponectin; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D018398:Homeodomain Proteins; D017466:Receptors, Endothelin; D015534:Trans-Activators; D014579:Urotensins; C084010:pancreatic and duodenal homeobox 1 protein