Methylenetetrahydrofolate Reductase (MTHFR) (C677T and A1298C) Polymorphisms and Vascular Complications in Patients with Type 2 Diabetes.
OBJECTIVE
To assess whether 2 polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, are risk factors for vascular complications in Tunisian patients with type 2 diabetes mellitus.


METHODS
The MTHFR polymorphisms were genotyped, and plasma homocysteine levels were evaluated in 160 Tunisian patients with type 2 diabetes mellitus.


RESULTS
Prevalence of the 2 heterozygous polymorphisms of the thermolabile MTHFR gene (CT and AC) was encountered more commonly in patients with diabetes mellitus than in the healthy controls (p<10-3). Subjects with diabetes had significantly higher homocysteine (Hcy) levels than the control subjects; however, there was no statistical difference in plasma Hcy values between carriers of mutant genotypes (CT/TT for C677T and AC/CC for A1298C) and wild types (CC and AA) in patients with diabetes. Retinopathy was found to be a vascular complication in patients with either the 677CT or the 1298(AC+CC) genotype more commonly than in those with the wild-type genotypes (p=0.003; OR=3.2, 95% CI, 1.4 to 7.4; p<10-3; OR=5.9, 95% CI, 2.7 to 13). Only patients who carry the A1298C mutation (AC+CC) are at risk for at least 1 complication (p=0.002). Double heterozygous mutants were at the greatest risk for retinopathy and for suffering at least 1 complication (p<10-3).


CONCLUSIONS
Studies involving a larger study population and various ethnic groups are required before ruling out the role of MTHFR gene in type 2 diabetes mellitus and in vascular complications.
Laboratory of Molecular Biology, Department of Hematology, Military Hospital of Tunisia, Tunis, Tunisia. Electronic address: fnajiba@yahoo.fr.
Najiba
N
Fekih-Mrissa
Laboratory of Molecular Biology, Department of Hematology, Military Hospital of Tunisia, Tunis, Tunisia.
Meriem
M
Mrad
Department of Endocrinology, Military Hospital of Tunisia, Tunis, Tunisia.
Hazard
H
Ibrahim
Laboratory of Molecular Biology, Department of Hematology, Military Hospital of Tunisia, Tunis, Tunisia.
Imen
I
Akremi
Laboratory of Molecular Biology, Department of Hematology, Military Hospital of Tunisia, Tunis, Tunisia.
Aicha
A
Sayeh
Department of Endocrinology, Military Hospital of Tunisia, Tunis, Tunisia.
Amel
A
Jaidane
Department of Endocrinology, Military Hospital of Tunisia, Tunis, Tunisia.
Haroun
H
Ouertani
Department of Endocrinology, Military Hospital of Tunisia, Tunis, Tunisia.
Borni
B
Zidi
Laboratory of Molecular Biology, Department of Hematology, Military Hospital of Tunisia, Tunis, Tunisia.
Nasreddine
N
Gritli
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014652:Vascular Diseases / Q000453:epidemiology* / Q000235:genetics*
C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
MTHFR gene; complications vasculaires; diabète sucré de type 2; genetic predisposition; gène MTHFR; homocystein; homocystéine; prédisposition génétique; type 2 diabetes mellitus; vascular complications