The association between end-stage diabetic nephropathy and methylenetetrahydrofolate reductase genotype with macroangiopathy in type 2 diabetes mellitus.
The T/T genotype of the methylenetetrahydrofolate reductase C677 T gene polymorphism is associated with elevated homocysteine levels and presumably with increased atherosclerotic risk. We evaluated the interaction between this gene polymorphism and end-stage diabetic nephropathy on the observed prevalence of macroangiopathy in type 2 diabetes mellitus. The methylenetetrahydrofolate reductase 677 C/T genotypes were determined in 174 type 2 diabetic patients: 80 with and 94 without renal failure due to diabetic nephropathy. In the patients with renal failure, the T/T genotype and T allele were significantly associated with macroangiopathy (T/T; 31 % vs. 2 %, P = 0.0001 T allele; 59 % vs. 29 %, P = 0.00014), whereas the associations were not significant in the patients without renal failure. In the multiple logistic regression analysis, age (10 years OR 4.05 [1.79 - 9.31], P < 0.0005) and 677 T allele (6.84 [2.12 - 22.05], P = 0.0013) were significantly associated with macroangiopathy in the patients with renal failure. In conclusion, this study demonstrated that the 677 T/T genotype and T allele of MTHFR were significantly associated with macroangiopathy in type 2 diabetic patients with renal failure. The MTHFR 677 T allele, together with renal dysfunction due to diabetic nephropathy, could be a strong risk factor for atherosclerotic disease.
Hasegawa
G
G
The First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. goji@koto.kpu-m.ac.jp
Obayashi
H
H
Kamiuchi
K
K
Nakai
M
M
Kanatsuna
T
T
Yamaguchi
M
M
Tanaka
T
T
Shigeta
H
H
Fujii
M
M
Yoshikawa
T
T
Nakamura
N
N
D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000209:etiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged
D042965:Methylenetetrahydrofolate Reductase (NADPH2)