Renal Insufficiency in Non-Diabetic Subjects: Relationship of MTHFR C677t Gene Polymorphism and Left Ventricular Hypertrophy

Abstract

Background: Association of methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism with hyperhomocysteinemia, renal failure, and cardiovascular events is controversial. We investigated the relationship of MTHFR 677C>T polymorphisms with left ventricular hypertrophy (LVH) and renal insufficiency. Methods: Glomerular filtration rate (GFR) and left myocardial ventricular mass/m2 were assessed in 138 non-diabetic subjects (age, 50.93 ± 14.85 years; body mass index, 27.95 ± 5.98 kg/m²), 38 no-mutation wild MTHFR C677CC, 52 heterozygous MTHFR C677CT, and 48 homozygous MTHFR C677TT, all with adequate adherence to current international healthy dietary guidelines. Serum homocysteine, insulin resistance, high-sensitivity C-reactive-protein (hsCRP), parathyroid hormone, and renal artery resistive index (RRI) were challenged by odds ratio analysis and multiple linear regression models. Results: MTHFR 677C>T polymorphism showed higher GFR (73.8 ± 27.99 vs. 58.64 ± 29.95; p= 0.001) and lower renal failure odds (OR, 0.443; 95% confidence interval, 0.141–1.387) in comparison with wild MTHFR genotype. A favorable effect on GFR of MTHFR polymorphism is presented independently by the negative effects of LVH, increased intra-renal arterial resistance, and hyperparathyroidism; GFR is the significant predictive factor to LVH. Conclusions: Renal insufficiency in non-diabetic subjects is explained by interactions of MTHFR C677T polymorphism mutation with LVH, hsCRP, intact parathyroid hormone (iPTH), and RRI. Sign of these predictive effects is opposite: subjects with MTHFR 677C>T polymorphism have lower likelihood of renal insufficiency; differently, wild-type MTHFR genotype subjects have lower GFR and greater hsCRP, iPTH, RRI, and LVH.

• homocysteine
• GFR
• renal function
• Mediterranean diet
• genetic
• MTHFR polymorphism
• insulin resistance
• obesity
• left ventricular hypertrophy
• echocardiography

ACKNOWLEDGMENT

These results were presented in part at the American Society for Nutrition 76th Annual Meeting held in San Diego, CA, April 21–25, 2012, and published as abstract on FASEB J (2012) 26: lb328

Declaration of interest: No conflict of interests that might lead to bias is declared by any of the Authors.

No grant or financial support, Public, Institutional or Private, was received by any Author for this or any related research, study, or activity.