Methylenetetrahydrofolate reductase gene polymorphism and susceptibility to diabetic nephropathy in type 1 diabetes
| Autor: | James H. Warram, Dariusz Moczulski, Jacek Bochenski, Andrzej S. Krolewski, Yuichiro Makita, Adam M. Smiles |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male medicine.medical_specialty Hyperhomocysteinemia Genotype Gastroenterology Nephropathy Diabetic nephropathy Gene Frequency Internal medicine Diabetes mellitus medicine Humans Diabetic Nephropathies Genetic Predisposition to Disease Allele frequency Methylenetetrahydrofolate Reductase (NADPH2) Type 1 diabetes Polymorphism Genetic biology business.industry Case-control study Middle Aged medicine.disease Proteinuria Endocrinology Diabetes Mellitus Type 1 Amino Acid Substitution Nephrology Methylenetetrahydrofolate reductase Case-Control Studies biology.protein Kidney Failure Chronic Female business Follow-Up Studies |
| Zdroj: | American journal of kidney diseases : the official journal of the National Kidney Foundation. 41(6) |
| ISSN: | 1523-6838 |
| Popis: | 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 ). Conclusion: 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. |
| Databáze: | OpenAIRE |
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