title: Association of a polymorphism of CYP3A4 with type 2 diabetes mellitus.
abstract: Although several environmental factors, including a high-calorie diet and physical inactivity, influence the development of type 2 diabetes mellitus, genetic factors have been shown to contribute to individual susceptibility to this condition. The purpose of the present study was to identify gene polymorphisms that confer susceptibility or resistance to type 2 diabetes mellitus, and thereby to contribute to assessment of the genetic risk for this condition. The study population comprised 5259 unrelated Japanese individuals (2980 men, 2279 women), including 1640 subjects with type 2 diabetes mellitus (1071 men, 569 women) and 3619 controls (1909 men, 1710 women). The genotypes for 94 polymorphisms of 67 genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the chi-square test revealed that the 13989-->G (Ile118Val) polymorphism of the cytochrome P450, subfamily IIIA, polypeptide 4 gene (CYP3A4) was significantly (false discovery rate, 0.000009) associated with the prevalence of type 2 diabetes mellitus. Multivariable logistic regression analysis with adjustment for age and sex also revealed that the 13989-->G (Ile118Val) polymorphism of CYP3A4 was significantly (P=0.00002) associated with the prevalence of type 2 diabetes mellitus, with the AG genotype being protective against this condition. Genotyping for CYP3A4 may thus prove informative for assessment of the genetic risk for type 2 diabetes mellitus.
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan. yamada@gene.mie-u.ac.jp
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Matsuo
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yajima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hibino
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yokoi
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
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: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
mesh_terms: D044466:Asian People / Q000235:genetics; D016009:Chi-Square Distribution; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human