title: Genetic risk for myocardial infarction in Japanese individuals with or without chronic kidney disease.
abstract: Although chronic kidney disease (CKD) is recognized as an important risk factor for myocardial infarction (MI), genetic factors underlying predisposition to MI in individuals with or without CKD remain largely unknown. The aim of the present study was to identify genetic variants that confer susceptibility to MI in individuals with or without CKD in order to allow prediction of genetic risk for such individuals separately. The study population comprised a total of 4344 individuals, including 1247 individuals with CKD (506 subjects with MI and 741 controls) and 3097 individuals without CKD (833 subjects with MI and 2264 controls). The 150 polymorphisms examined in this study were selected by genome-wide association studies of ischemic stroke and MI with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix) and determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. In individuals with CKD, no polymorphism was significantly related to MI. In individuals without CKD, an initial screen by the Chi-square test revealed that the Cyright curved arrow T polymorphism of CLEC16A (rs9925481) and the Aright curved arrow G polymorphism of LAMA3 (rs12373237) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the Cright curved arrow T polymorphism of CLEC16A (dominant model; P=0.0003; odds ratio, 0.66) and the Aright curved arrow G polymorphism of LAMA3 (recessive model; P=0.0087; odds ratio, 0.75) were significantly (P<0.05) associated with MI. A stepwise forward selection procedure also revealed that these polymorphisms were significant and independent determinants of MI. CLEC16A and LAMA3 may be susceptibility loci for MI in Japanese individuals without CKD. Determination of genotypes for CLEC16A and LAMA3 may prove informative for assessment of the genetic risk for MI in such individuals.
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yokoi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yoshida
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Norifumi
authors.initials: N
authors.lastname: Metoki
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors