Case Control Study
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World J Nephrol. Feb 6, 2015; 4(1): 127-137
Published online Feb 6, 2015. doi: 10.5527/wjn.v4.i1.127
Relationship of MTHFR gene polymorphisms with renal and cardiac disease
Francesca M Trovato, Daniela Catalano, Angela Ragusa, G Fabio Martines, Clara Pirri, Maria Antonietta Buccheri, Concetta Di Nora, Guglielmo M Trovato
Francesca M Trovato, Daniela Catalano, Clara Pirri, Concetta Di Nora, Guglielmo M Trovato, Department of Internal Medicine, University of Catania, 95100 Catania, Italy
Angela Ragusa, Maria Antonietta Buccheri, AOU Prenatal Diagnosis and Medical Genetics, University of Catania, 95100 Catania, Italy
G Fabio Martines, Internal and Emergency Medicine Department, University of Catania, 95100 Catania, Italy
Author contributions: All the authors solely contributed to this paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Guglielmo M Trovato, MD, Department of Internal Medicine, University of Catania, P.A. Via Sant’Orsola 30, 95100 Catania, Italy. trovato.eu@gmail.com
Telephone: +39-95-3781533 Fax: +39-95-3781549
Received: April 21, 2014
Peer-review started: April 21, 2014
First decision: June 27, 2014
Revised: November 7, 2014
Accepted: November 17, 2014
Article in press: November 19, 2014
Published online: February 6, 2015
Processing time: 292 Days and 8.4 Hours
Abstract

AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial.

METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms.

RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism.

CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism.

Keywords: Homocysteine; Glomerular filtration rate; Renal function; Mediterranean diet; Genetic; Methylenetetrahydrofolate reductase polymorphism; Insulin resistance; Obesity; Left ventricular hypertrophy; Echocardiography

Core tip: We investigated the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial, and challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism.