title: The -822G/A polymorphism in the promoter region of the MAP4K5 gene is associated with reduced risk of type 2 diabetes in Chinese Hans from Shanghai.
abstract: MAP4K5 (mitogen-activated protein kinase kinase kinase kinase 5), an early component of MAP kinase signal cascades was shown to activate Jun kinase in mammalian cells. The association between SNPs of MAP4K5 and type 2 diabetes (T2DM) was investigated due to the known relationship of the JNK pathway with T2DM. A total of 1,399 cases were included in the study. Oral glucose tolerance test (OGTT) and insulin release test (IRT) were performed, and blood DNA samples were extracted and genotyped on the MAP4K5 -822G/A site. These cases were subdivided into central-obesity and nonobesity groups, based upon their individual waist circumference. Allele-specific real-time PCR was employed for genotyping. No difference was found between the two groups in the distribution of three genotypes on MAP4K5 -822G/A. In the central-obesity group, fewer diabetic patients (38.9%) were present in the AA genotype group than the GG/GA group (58.5%, P=0.024). Glucose levels after 30 and 60 min of 75 g glucose tolerance, area under the curve for glucose, and insulin secretion indexes were lower (P<0.05) in AA than those in GG/GA genotype group in the central-obesity cases. Other variables did not show significant differences between the two groups. In the Han population from Shanghai, the AA genotype of MAP4K5 -822G/A in central-obesity cases appears less likely to develop diabetes compared with the other genotypes. Therefore, the G allele may be a factor that does not protect central-obesity cases from developing into diabetes.
authors.affiliation: School of Medicine, Ruijin Hospital, Endocrine and Metabolic Disease Deparment, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai JiaoTong University, People's Republic China. yanyungu@yahoo.com.cn
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Gu
authors.forename: Tianhong
authors.initials: T
authors.lastname: Luo
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Dai
authors.forename: Weixia
authors.initials: W
authors.lastname: Jian
authors.forename: Sheng
authors.initials: S
authors.lastname: Zheng
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Zhou
authors.forename: Weibin
authors.initials: W
authors.lastname: Zhou
authors.forename: Yixing
authors.initials: Y
authors.lastname: Wu
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Youping
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiping
authors.initials: J
authors.lastname: Li
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xie
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Luo
mesh_terms: D000328:Adult; D000483:Alleles; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D002681:China / Q000453:epidemiology; D004247:DNA / Q000097:blood / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D014505:Urban Population
chemical_list: D001786:Blood Glucose; D007328:Insulin; D004247:DNA; C404144:MAP4K5 protein, human; D017346:Protein Serine-Threonine Kinases