Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end-stage diabetic nephropathy

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2007-01, Vol.22 (1), p.154-162
• Main Authors: Böger, Carsten A., Stubanus, Mike, Haak, Thomas, Götz, Angela K., Christ, Johanna, Hoffmann, Ute, Riegger, Günter A. J., Krämer, Bernhard K.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Associated diseases and complications; Biological and medical sciences; cardiovascular mortality; Cohort Studies; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - mortality; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - genetics; Diabetic Nephropathies - mortality; Dietary Supplements; Disease Progression; Emergency and intensive care: renal failure. Dialysis management; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; ESRD; Female; genetics; Genotype; Glomerulonephritis; Homocysteine - blood; Humans; Intensive care medicine; Kidney Failure, Chronic - complications; Male; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - physiology; MTHFR (C677T) polymorphism; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Phenotype; Polymorphism, Single Nucleotide; progression of diabetic nephropathy; Time Factors; type 2 diabetes mellitus
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfl512

Background. The MTHFR C677T single nucleotide polymorphism TT genotype is associated with increased levels of plasma homocysteine and possibly an effect on cardiovascular mortality. We evaluated the effect of C677T genotype on mortality in a large end-stage renal disease (ESRD) cohort. Methods. C677T genotype was determined in 439 Caucasians with end-stage diabetic nephropathy (DNP) (cases) recruited from 30 dialysis centres in Southern Germany. A total of 482 type 2 diabetes patients without DNP (no microalbuminuria) at inclusion served as a genotype control collective. Patients were prospectively followed for 4 years. Primary endpoint was all-cause mortality. Results. In contrast to controls, the genotype distribution in cases was not in Hardy–Weinberg equilibrium (HWE, P = 0.003), due to a less than expected number of patients with the TT genotype. The requirements of HWE were met in cases with 0.05), or with an increased rate of progression to novel microalbuminuria. Conclusion. MTHFR 677TT genotype was significantly underrepresented in patients with ESRD in our study, but was not associated with premature mortality in these patients. We found no evidence for survival bias due to C677T genotype in the ESRD cohort, or bias due to genetically determined accelerated progression to novel microalbuminuria in the controls. However, we cannot exclude that the TT genotype protects from progression from microalbuminuria to more advanced stages of DNP, or that TT genotype is associated with premature mortality before a patient progresses to ESRD.