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.