Association of ACE and MTHFR genetic polymorphisms with type 2 diabetes mellitus: Susceptibility and complications.

HYPOTHESIS/INTRODUCTION: Polymorphisms of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes have been proposed to be associated with type 2 diabetes mellitus (T2DM) with conflicting results. This work was planned in order to check for the association of these polymorphisms with the susceptibility for and complications of T2DM among Egyptian cases. MATERIALS AND METHODS: This is a case controlled study involving 203 patients with T2DM and 311 healthy controls. Polymorphic variants of ACE I>D and MTHFR (677 C>T and 1298 A>C) were determined using the polymerase chain reaction (PCR) restriction analysis technique. RESULTS: The susceptibility to T2DM was higher among subjects having the MTHFR 677TT (odds ratio (OR)=2.2, p=0.01), MTHFR 1298 AA (OR=1.84, p=0.001) and ACE (ID+II) (OR=2.0, p=0.0007) genotypes. Logistic regression analysis showed that MTHFR 677T allele was a risk factor for diabetic retinopathy (DR) (OR=3.47, p<0.001), diabetic polyneuropathy (DPN) (OR=5.2, p<0.0001) and ischemic heart disease (IHD) (OR=2.9, p<0.05), while MTHFR 1298 C allele was a risk factor for DR (OR=4.2, p<0.001) and the ACE DD genotype was a risk factor for DPN (OR=3.1, p<0.001). CONCLUSIONS: The MTHFR 677 TT genotype was associated with T2DM susceptibility and complications (DR, DPN and IHD). The MTHFR 1298 CC, AC and ACE DD genotypes were associated with DR and DPN.

MTHFR C677T, A1298C and ACE I/D polymorphisms as risk factors for diabetic nephropathy among type 2 diabetic patients.

BACKGROUND: Genetic variations have been proposed to play a role in the susceptibility to diabetic nephropathy. OBJECTIVES: To check for the association of genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE) genes with the development of diabetic nephropathy among type 2 diabetic patients. METHODS: Participants comprised 202 patients with type 2 diabetes, of whom 102 were affected with diabetic nephropathy. Genetic variants corresponding to MTHFR C677T, A1298C and ACE I/D genotypes were determined using the PCR technique coupled with digestion and restriction analysis. RESULTS: Cases with diabetic nephropathy had a significantly higher frequency of the MTHFR 677 TT, 677 CT, ACE DD mutant genotypes compared with diabetic cases without nephropathy. Analysis of the association of studied MTHFR C677T, A1298C and ACE I/D polymorphisms with albuminuria showed that the MTHFR 677 T polymorphism, in the recessive and dominant models, was a risk factor for both micro and macroalbuminuria, while the ACE DD mutant genotype was a risk factor for microalbuminuria and the MTHFR 1298C in the dominant model only was a risk factor for macroalbuminuria. CONCLUSION: These findings indicate that ACE and MTHFR genetic polymorphisms might be considered as genetic risk factors for diabetic nephropathy among patients with type 2 diabetes.