Gender differences in the association of gene polymorphisms with type 2 diabetes mellitus.
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.
Yamaguchi
Sachiyo
S
Department of Human Functional Genomics, Life Science Research Center, Mie University, Mie 514-8507, Japan.
Yamada
Yoshiji
Y
Matsuo
Hitoshi
H
Segawa
Tomonori
T
Watanabe
Sachiro
S
Kato
Kimihiko
K
Yokoi
Kiyoshi
K
Ichihara
Sahoko
S
Metoki
Norifumi
N
Yoshida
Hidemi
H
Satoh
Kei
K
Nozawa
Yoshinori
Y
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
D052242:Adiponectin; D043303:Aryldialkylphosphatase; D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D019699:Thrombospondins; D000099262:Thrombospondin 2; C468406:PON1 protein, human