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Aims: Diabetes has become a major public health problem in China. Recent advances in genetic studies have identified numerous susceptibility loci for type 2 diabetes (T2D). Current models to detect risk of T2D are largely based on studies from European populations; this study aims to replicate those efforts in a Chinese population from the Ningbo region in order to diversify and fortify risk models. Methodology: We successfully genotyped 11 single nucleotide polymorphisms (SNPs) in 222 subjects with T2D and 140 subjects with normal glucose regulation in a population from the Ningbo region of China. Additive and dominant models were used to analyze the associations between SNPs and T2D. Results: Adjusting for age, triglycerides, total cholesterol, low density lipoprotein, and BMI in the dominant model, we identified three SNPs which were associated T2D: CDKAL1 (OR=2.29 [95%CI=1.25-4.19]), KCNQ1 (4.22 [1.79-9.99]), and IGF2BP2 (1.76 [1.06-2.94]). No significant association was found between T2D and SNPs from KCNJ11, PPARG, TCF7L2, SALC30A8, CDKN2B, HHEX, HNF1β, and WFS1. Conclusion: Our data indicates that in this population, CDKAL1, KCNQ1, and IGF2BP2 are T2D susceptibility genes.
RESUMO
Objective Type 2 diabetes mellitus ( T2DM) as a common disease around the world becomes a great threat to the health of human beings.The cynomolgus T2DM model, which preferably simulates human T2DM onset and progress, can be beneficial to the drug development and clinical treatment.In the present study, 37 of T2DM-susceptibility SNPs and the extended genome sequences were used to obtain corresponding SNPs in the T2DM cynomolgus monkeys. Methods Firstly, DNA pool screening was conducted.Then, using polymerase chain reaction to amplify and to sequence the cynomolgus homologous sequences.Using DNAStar software to analyze the differences between bases.Finally, we used analysis of variance and F test to calculate the frequency of alleles.We also used the GLM models of SAS software to analyze the association of genotype with fasting plasma glucose and glycosylated hemoglobin.Results SNP661A,SNP661B, SNP343A, SNP343B, SNP343C, SNP565A, SNP565B and SNP565C were found to have a significant difference of allele frequencies between spontaneous cases and controls.Conclusions The findings of this study suggest that SNP661A, SNP661B, SNP343A, SNP343B and SNP343C may play an important role in the establishment of cynomolgus T2DM models.
RESUMO
Type 1 diabetes, a complex genetic disease, is determined by both genetic and environmental factors. After excluding the five susceptibility loci discovered by genetic linkage studies and candidate-gene association studies, more than 30 new susceptibility loci have been found to be related with type 1 diabetes as a result of genome-wide association study.