Association of Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism with Type 2 Diabetic Nephropathy in Gaza Strip-Palestine

Abstract

Introduction: The insertion/deletion (I/D) polymorphism of 287 bp Alu repeat sequence in intron 16 of Angiotensin Converting Enzyme (ACE) gene resulting in three genotypes I/D, D/D and I/I. ACE gene expression is associated with ACE levels in cells and in the plasma. It indicated that the polymorphism may modulate the expression of the ACE gene. The D/D genotype is believed to confer deleterious effect to many pathogenesis, also, it might be a cause-effect for type 2 diabetic nephropathy (T2DN). In this study, we evaluated the frequency of the different genotypes of ACE gene and investigated if there is an association between ACE gene polymorphism and T2DN by comparing the genotypes results of T2DN patients to healthy control, Type 2 diabetes mellitus (T2DM) and nephropathy patients in Gaza Strip.
 Methodology: The study included 170 subjects, consisting of 43 T2DM patients undergoing dialysis "T2DN" compared to 41 T2DM patients who were not undergoing dialysis, 43 patients undergoing dialysis without T2DM and 43 healthy individuals. Blood samples were collected in EDTA tubes for DNA extraction. Polymerase Chain Reaction (PCR) was used to detect ACE gene polymorphism. All subjects were asked to fill the questionnaire interview.
 Results and Conclusion: The initial results showed that there is no statistically significant association between ACE genotypes and T2DN, also between the T2DM and nephropathy when compared to the healthy control (p> 0.05). The (D/D) genotype was the most frequent in all study groups. Moreover, no association was observed between ACE genotypes and gender, diabetic nephropathy, nephropathy, diabetes, hypertension, obesity and various other diabetes complications.

Determination of Glyoxalase-1 levels and Identification of Genetic Variants in GLO1 Gene in Patients of Diabetic Nephropathy

“…In the literature, some other genes have been explored for association with DN e.g. (1) Toll-like receptor (TLR ) gene mutations have been linked with the development of kidney disease, 24 (2) Angiotensin-converting enzyme ( ACE ) insertion-deletion polymorphism has also been linked with the development of diabetic nephropathy 25 (3) Another study looked for endothelial nitric oxide synthase gene ( G894T, 4b/a, and T786C ) polymorphism and development of diabetic nephropathy. 26 Genes, for example, that for catalase, related to oxidative stress are associated with diabetes and nephropathy independently.…”