Methylenetetrahydrofolate reductase gene polymorphism and susceptibility to diabetic nephropathy in type 1 diabetes.
BACKGROUND
The T allele of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with elevated plasma homocysteine levels, and it has been postulated to be a risk factor for the development of diabetic nephropathy. We examined this hypothesis in both a case-control and a follow-up study in individuals with type 1 diabetes.


METHODS
In the case-control study, the control group included 310 subjects with normoalbuminuria and diabetes duration of 15 years or greater, and the case group included 88 prevalent cases with end-stage renal disease (ESRD). The follow-up study included 235 subjects with overt proteinuria followed up for 6 years (on average), during which time ESRD developed in 69 subjects. DNA from each individual was genotyped for the C677T MTHFR polymorphism.


RESULTS
The frequency of TT homozygotes did not vary significantly among the four groups: 10% in controls, 15% in prevalent cases of ESRD, 13% in cases with new-onset ESRD, and 11% in those who remained proteinuric during follow-up (P = 0.9, 6 df). Similarly, frequency of the T allele varied little among the same groups (range, 33% to 36%; P = 0.9, 3 df) During follow-up, 52 of 323 individuals with diabetic nephropathy died. Total mortality rates were 4.3/100 person-years in TT homozygotes, 2.4/100 person-years in CT heterozygotes, and 3.0/100 person-years in CC homozygotes (P = 0.55, 2 df).


CONCLUSIONS
Using both a large case-control and a follow-up study, we found no evidence that the C677T MTHFR polymorphism has a significant role in the development of diabetic nephropathy in type 1 diabetes.
Makita
Yuichiro
Y
Research Division, Joslin Diabetes Center, Boston, MA 02215-5397, USA.
Moczulski
Dariusz K
DK
Bochenski
Jacek
J
Smiles
Adam M
AM
Warram
James H
JH
Krolewski
Andrzej S
AS
D000328:Adult; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000201:enzymology / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011507:Proteinuria / Q000235:genetics
D042965:Methylenetetrahydrofolate Reductase (NADPH2)