title: Gender differences in the association of gene polymorphisms with type 2 diabetes mellitus.
abstract: Type 2 diabetes mellitus is a complex metabolic disorder in which endogenous sex hormones may contribute to sex-dependent etiologies. We hypothesized that genetic variants related to type 2 diabetes mellitus might differ between men and women. We thus performed a large-scale association study to identify gene polymorphisms associated with type 2 diabetes mellitus in men and women separately. The study population comprised 4854 unrelated Japanese individuals (2688 men, 2166 women), including 1490 subjects with type 2 diabetes mellitus (969 men, 521 women). The genotypes for 16 gene polymorphisms were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis with adjustment for age, body mass index, and smoking status revealed that the T-->G (3' UTR) polymorphism of the thrombospondin 2 gene (THBS2), the -603A-->G polymorphism of the coagulation factor III gene (F3), and the G-->T (intron 2) polymorphism of the adipocyte, C1Q, and collagen domain containing (adiponectin) gene (ADIPOQ) were significantly associated with the prevalence of type 2 diabetes mellitus in men, and that the A-->G (Arg160Gly) polymorphism of the paraoxonase 1 gene (PON1) was significantly associated with this condition in women. A stepwise forward selection procedure demonstrated that genotypes of THBS2, F3, and ADIPOQ were significant determinants of type 2 diabetes mellitus in men, and that genotype of PON1 significantly affected this condition in women. Genotyping of these polymorphisms may prove informative for assessment of the genetic component of type 2 diabetes mellitus for men and women separately.
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Mie 514-8507, Japan.
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Matsuo
authors.forename: Tomonori
authors.initials: T
authors.lastname: Segawa
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
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: D052242:Adiponectin / Q000235:genetics*; D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D058966:Contactins; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012737:Sex Factors; D019699:Thrombospondins / Q000235:genetics*; D000099262:Thrombospondin 2
chemical_list: D052242:Adiponectin; D043303:Aryldialkylphosphatase; D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D019699:Thrombospondins; D000099262:Thrombospondin 2; C468406:PON1 protein, human