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


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.
Genetics Unit, Mansoura University, Egypt settin@mans.edu.eg.
Ahmad
A
Settin
Genetics Unit, Mansoura University, Egypt.
Rizk
R
El-Baz
Zoology Department, Mansoura University, Egypt.
Azza
A
Ismaeel
Zoology Department, Mansoura University, Egypt.
Wafaa
W
Tolba
Zoology Department, Mansoura University, Egypt.
Wafaa A
WA
Allah
D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
ACE gene; MTHFR gene; diabetic neuropathy; diabetic retinopathy; type 2 diabetes