| Type 2 diabetes is a multigene hereditary disease and the genetic factors have a significant impact. With the development of sequencing technique, more and more novel susceptibility loci of type 2 diabetes have been discovered all over the world. The SNP rs12571751 in ZMIZ1 gene was identified as a T2D susceptibility locus in European descent and Japanese populations. However, this observation has not been replicated in Chinese Han population. GDNF was founded as a neurotrophic factor initially, while researchers showed this protein was also associated wih the development of islet, the ?-cell proliferation, mass and apoptosis, glucose homeostasis and glucose tolerance which indicated GDNF gene could be related to the risk of type 2 diabetes. In the SNPs of GDNF gene, rs884344 was associated with depresion, which indicated the SNP have important genetic effect.The aim of this study was to explore the associations of rs12571751 in ZMIZ1 and rs884344 in GDNF with type 2 diabetes and some related clinical traits in Chinese Han population via the TaqMan allelic discrimination assays and statistic analyses.The main contents of this paper are as follows:1. A total of 870 unrelated Chinese individuals residing in Nanjing city Jiangsu Province were recruited according to the inclusive and exclusive criteria. The participants were divided into three groups that were control group, prediabetes group and T2D group according to the WHO criteria for diabetes. We conducted a detailed clinical investigation of all the participants including anthropometric and biochemical traits. Anthropometric measurements were comprised of height, weight, waist and hip circumferences to calculate BMI and waist hip ratio (WHR). Biochemical traits of participants included fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and glycated hemoglobin (HbAlc).This part was finished by our group.2. Genomic DNA was extracted from venous blood by the Blood DNA System Kit. The concentration and purity of DNA samples were detected by a spectrometer and the results of OD260/OD280 showed qualified concentration and purity of DNA samples. The SNPs rs12571751 and rs884344 were genotyped using TaqMan allelic discrimination assays and the genotyping was performed by the Real-time fluorescent quantitative PCR system. The genotype discrimination plots of SNPs showed that plots representing three different genotypes emerged in three lines which indicated the specificity of probes and the veracity of genotype discrimination.3. Statistic analyses were performed to analyze the the associations of the rs 12571751 in ZMIZ1 with type 2 diabetes, related clinical traits and obesity. The clinical characteristics of all participants were showed in this study. The genotype distributions of the SNP were in accord with Hardy-Weinberg equilibrium and indicated the samples were representative. The Pearson's x2 tests showed no significant differences in allele or genotype frequency distribution among T2D, prediabetes and control groups (P>0.05). The results of multiple logistic regression declared no association between genotype distribution and type 2 diabetes with adjustment for sex, age and BMI as covariates (P=0.517, P=0.755). The results of one-way ANOVA indicated no significant differences in BMI, WHR, FPG, PPG or HbAlc among different genotype groups (P>0.05). The multiple linear regression results showed that the genotype frequency distribution was not associated with BMI (P=0.927), WHR (P=0.104), FPG (P=0.858), PPG (P=0.953) and HbAlc (P=0.981).This locus was not founded associated with obesity (P>0.05).4. The statistical methods to analyze the the associations of the rs884344 in GDNF with type 2 diabetes, related clinical traits and obesity were same as above. The genotype distributions of the rs884344 were also in accord with Hardy-Weinberg equilibrium. The Pearson's x2 tests showed no association between allele or genotype frequency distribution with type 2 diabetes (P=0.484 and P=0.664 respectively). Adjusting for sex, age and BMI, the multiple logistic regression result showed the genotype distribution was not associated with type 2 diabetes (P=0.603,P=0.827). The one-way ANOVA results indicated no significant differences in BMI, WHR, FPG, PPG or HbAlc among different genotype groups (P>0.05). The results of multiple linear regression results showed the genotype frequency distribution was not associated with BMI (P=0.601), WHR (P=0.412), FPG (P=0.115), PPG (P=0.379) and HbAlc (P=0.239). Pearson's ?2 test and multiple logistic regression results declared no assciation of the lucus with obesity (P>0.05).In conclusion, we did not find the SNPs rs12571751 in ZMIZ1 and rs884344 in GDNF were associated with type 2 diabetes in Chinese Han population. There were no associations of this two loci with BMI, waist hip ratio, fasting plasma glucose, postprandial plasma glucose and HbAlc or obesity. |
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