Polymorphisms of the ApoE, HSD3B1, IL-1beta and p53 genes are associated with the development of early uremic complications in diabetic patients: results of a DNA resequencing array study.

摘要

Genetic polymorphisms of the genes involved in angiogenesis, the inflammatory cascade or apoptosis control can influence the chronic complications of diabetic patients. Parallel evaluation of multiple genetic polymorphisms became available with the development of DNA resequencing arrays. We aimed to develop a 16-gene, 18,859-nucleotide resequencing array to analyze the genetic background of uremic and gastrointestinal complications. DNA was isolated from 10 ml of peripheral blood of 41 non-uremic and 37 uremic patients with type II diabetes mellitus (DM); 32 suffering from gastric erosion complications. An Affymetrix Customseq Resequencing array was developed containing a total of 37 PCR products of selected genes. Confirmatory analysis was performed for 5 known polymorphisms by RFLP and for 4 others by capillary sequencing. Statistical analysis was performed using the Fisher's exact test. Correlations between the DNA resequencing array and the confirmatory methods were 96% for RFLP and 99.4% for capillary sequencing. The genetic polymorphisms of the ApoE, HSD3B1, IL-1beta and p53 genes were found to be significantly different (p<0.05) between the uremic and non-uremic diabetes group. In regards to the gastric erosion complications of the diabetic uremic patients, the A17708T polymorphism of the p53 intron 10 was found to have a statistically significant (p<0.05) role. In conclusion, DNA sequencing arrays can contribute to a multiparameter genetic analysis yielding highly correlating results using a single method in patients suffering type II DM.