Are genetic variants of the methyl group metabolism enzymes risk factors predisposing to obesity?

Ileana Terruzzi, P. Senesi, I. Fermo, G. Lattuada, L. Luzi

Research output: Contribution to journalArticle

Abstract

Obesity, due to the combination of inherited genes and environmental factors, is continually increasing. We evaluated the relationship between polymorphisms of methylene-tetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), betaine:homocysteine methyltransferase (BHMT G742A) and cystathionine β-synthase (CBS 68-bp ins) genes and the risk of obesity. We studied these polymorphic variants in 54 normal and 82 obese subjects [body mass index (BMI)=22.4±1.8, 34.1±7.1; ages 35.2±10.7, 43.3±10.6 respectively]. Levels of total plasma homocysteine (t-Hcy), folates, and vitamins B6 and B12 were not significantly different, while leptin concentration was significantly higher (p=0.005) in the obese patients compared to the lean controls. The frequency of only (a) MTHFR (AC), (b) MTR (AG), and (c) MTRR (AG) heterozygous genotypes was statistically different in the obese compared to the control group (p=0.03, p=0.007, and p=0.01). Single (a), (b), and (c) heterozygous genotypes had a significant risk of developing obesity [p=0.02, 0.01, and 0.03; odds ratio (OR)=2.5, 3.0, and 2.4; 95% confidence interval (CI)=1.2-5.3, 1.3-7.1, and 1.2-5.1 respectively] and the risk remarkably increased for combined genotypes a+b, a+c, b+c, and a+b+c (p=0.002, 0.002, 0.016, 0.006; OR=7.7, 5.4, 5.8, 15.4; 95% CI=1.9-30.4, 1.7-16.8, 1.4-23.2, 1.6-152.3). These findings suggest that in obese subjects, Hcy cycle efficiency is impaired by MTHFR, MTR, and MTRR inability to supply methyl-group donors, providing evidence that MTHFR, MTR, and MTRR gene polymorphisms are genetic risk factors for obesity.

Original languageEnglish
Pages (from-to)747-753
Number of pages7
JournalJournal of Endocrinological Investigation
Volume30
Issue number9
Publication statusPublished - Oct 2007

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Keywords

  • Betaine:homocysteine methyltransferase
  • Cystathionine β-synthase
  • Methionine synthase
  • Methionine synthase reductase
  • Methylene-tetrahydrofolate reductase
  • Polymorphism

ASJC Scopus subject areas

  • Endocrinology

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