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MTHFR A1298C polymorphism is associated with cardiovascular risk in end stage renal disease in North Indians

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Abstract

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 patients on hemodialysis. We performed case-control study involving107 patients with ESRD and 103 healthy controls. Plasma Hcy was measured in all the subjects and these subjects were genotyped for three MTHFR polymorphisms (C677T, A1298C, and G1793A). We observed significantly higher Hcy levels in patients as compared to controls. The frequency of MTHFR 1298CC genotype was significantly higher in ESRD patients than in controls (21.4% vs. 2.9%); the frequency of the MTHFR C677T genotypes did not differ between groups (26.1% vs. 17.4%). Compound heterozygous MTHFR 677CT/1298AC genotypes showed maximum association with the risk of ESRD (OR: 12.8; 5%CI: 1.64–10.01, P < 0.05). Concurrent occurrence of MTHFR 677CC wild genotype with either 1298CC or 1793GA significantly increased the risk of disease (OR: 7.20; 95%CI: 2.06–2.51, P < 0.001 and OR: 7.60; 95%CI: 1.68–34.35; P < 0.05, respectively). MTHFR 1298CC genotype was associated with higher Hcy levels. IMT was also significantly higher in patients with the 1298CC genotype (P < 0.05). Thus, A1298C polymorphism of MTHFR gene appears to be associated with the severity of carotid atherosclerosis and co-occurrence of MTHFR polymorphisms may be a risk factor for CVD in patients on hemodialysis.

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Authors and Affiliations

  1. Department of Experimental Medicine & Biotechnology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, 160012, India

    Aruna Poduri & Madhu Khullar

  2. Department of Nephrology, Post Graduate of Institute of Medical Education & Research (PGIMER), Chandigarh, India

    Debabrata Mukherjee, Kamal Sud, Harbir Singh Kohli & Vinay Sakhuja

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  1. Aruna Poduri
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  2. Debabrata Mukherjee
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Correspondence to Madhu Khullar.

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Poduri, A., Mukherjee, D., Sud, K. et al. MTHFR A1298C polymorphism is associated with cardiovascular risk in end stage renal disease in North Indians. Mol Cell Biochem 308, 43–50 (2008). https://doi.org/10.1007/s11010-007-9610-7

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