MTHFR C677T and A1298C Gene Polymorphisms, Hyper- homocysteinemia, and Intimal Medial Thickness as Risk Factors of End-Stage Renal Disease in Children on Hemodialysis

Background: The methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism has been shown to be associated with cardiovascular disease and in patients with end-stage renal disease (ESRD). However, the relationship between MTHFR polymorphisms and cardiovascular disease (CVD) in patients on hemodialysis has not been examined. The aim of this study was to assess the association of polymorphisms of MTHFR gene with homocysteine (Hcy) and intimal medial thickness (IMT) in children on hemodialysis. Methods: We performed a casecontrol study comprising 55 pediatric patients with ESRD and 55 healthy children as controls. Plasma Hcy was measured in all the subjects and these subjects were genotyped for 2 MTHFR polymorphisms (C677T and A1298C). Results: We observed significantly higher Hcy levels in patients compared to controls. The frequency of MTHFR 1298CC genotype was significantly higher in ESRD children than in controls (21.82 % vs 5.45 %) and the frequency of the MTHFR 677TT genotype differs significantly between groups (18.18 % vs 0.00 %). The frequency of co-occurrence of MTHFR 677CT/1298AC and 677TT/1298CC was significantly higher in patients than controls and was associated with an increased risk of disease (p < 0.05). MTHFR 1298AC+CC genotypes were associated with higher Hcy levels. IMT was also significantly higher in patients with the 1298AC+CC genotypes (p < 0.05). Conclusion: A1298C polymorphism of MTHFR gene appears to be associated with the severity of carotid atherosclerosis and co-occurrence of MTHFR polymorphisms has a synergistic effect on increased risk of disease susceptibility. J Clin Basic Cardiol 2012; 15 (online): 7–12.