Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome.
Metabolic syndrome is a risk factor for cardiovascular disease. The aim of the present study was to identify genetic variants that confer susceptibility to atherothrombotic cerebral infarction among individuals with metabolic syndrome in order to allow prediction of genetic risk for this condition. The study population comprised 1284 unrelated Japanese individuals with metabolic syndrome, including 313 subjects with atherothrombotic cerebral infarction and 971 controls. The genotypes for 296 polymorphisms of 202 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (P<0.05) with the prevalence of atherothrombotic cerebral infarction. Among these polymorphisms, the 2445G-->A (Ala54Thr) polymorphism of FABP2 was most significantly associated with this condition. Our results suggest that FABP2, IPF1, FABP1, ROS1, ADIPOQ, ALOX5AP, NOS3, and LGALS2 are susceptibility loci for atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome. Genotypes for these polymorphisms, especially for the 2445G-->A (Ala54Thr) polymorphism of FABP2, may prove informative for the prediction of genetic risk for atherothrombotic cerebral infarction among such individuals.
Yamada
Yoshiji
Y
FAHA, Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Mie 514-8507, Japan. yamada@gene.mie-u.ac.jp
Kato
Kimihiko
K
Oguri
Mitsutoshi
M
Yoshida
Tetsuro
T
Yokoi
Kiyoshi
K
Watanabe
Sachiro
S
Metoki
Norifumi
N
Yoshida
Hidemi
H
Satoh
Kei
K
Ichihara
Sahoko
S
Aoyagi
Yukitoshi
Y
Yasunaga
Akitomo
A
Park
Hyuntae
H
Tanaka
Masashi
M
Nozawa
Yoshinori
Y
D058927:5-Lipoxygenase-Activating Proteins; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002544:Cerebral Infarction / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D016009:Chi-Square Distribution; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005260:Female; D037501:Galectin 2 / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000208:ethnology / Q000209:etiology / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024821:Metabolic Syndrome / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011110:Polymorphism, Genetic; D015995:Prevalence; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; C493319:FABP1 protein, human; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D037501:Galectin 2; D018398:Homeodomain Proteins; C511926:LGALS2 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human