Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus.
OBJECTIVE
To find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.


METHODS
The MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP.


RESULTS
The possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p=0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p=0.027, and p=0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p<0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR=4.73, p=0.01).


CONCLUSIONS
Both MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.
Rahimi
Mehrali
M
Department of Endocrinology, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Hasanvand
Ali
A
Rahimi
Zohreh
Z
Vaisi-Raygani
Asad
A
Mozafari
Hadi
H
Rezaei
Mansour
M
Zargooshi
Javad
J
Najafi
Farid
F
Shakiba
Ebrahim
E
D000419:Albuminuria / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D003928:Diabetic Nephropathies / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007492:Iran; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D042965:Methylenetetrahydrofolate Reductase (NADPH2)