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© 2003 The American Society for Nutritional Sciences J. Nutr. 133:1281-1285, May 2003

Nutrient-Gene Interactions

The Interaction between MTHFR 677 C->T Genotype and Folate Status Is a Determinant of Coronary Atherosclerosis Risk

Domenico Girelli*,2, Nicola Martinelli*, Francesca Pizzolo*, Simonetta Friso*,{dagger}, Oliviero Olivieri*, Chiara Stranieri{ddagger}, Elisabetta Trabetti{ddagger}, Giovanni Faccini§, Elisa Tinazzi*, Pier Franco Pignatti{ddagger} and Roberto Corrocher*

* Department of Clinical and Experimental Medicine, {ddagger} Institute of Biology and Genetics, and § Institute of Clinical Chemistry, University of Verona, Policlinico G.B. Rossi, 37134 Verona, Italy and {dagger} Vitamin Metabolism Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research on Aging at Tufts University, Boston, MA 02111

2To whom correspondence should be addressed. E-mail: domenico.girelli{at}univr.it.

The 677 C->T polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene interacts with folate status in determining elevated total plasma levels of homocysteine, a risk factor for coronary atherosclerotic disease (CAD). The present study had the following goals: 1) to define the 677 C->T genotype-specific threshold values of both plasma and RBC folate, associated with hyperhomocysteinemia (>15 µmol/L); and 2) to determine the risk of CAD among subjects with levels of folate below the genotype-specific threshold considered at risk for hyperhomocysteinemia. We examined 655 subjects, with (433) or without (222) angiographically documented CAD. The MTHFR 677 C->T genotype-specific threshold values of plasma folate corresponded to the 40th, 30th and 10th percentile in the TT, CT and CC genotype, respectively. A multivariate logistic regression analysis showed that the risk of CAD among subjects with plasma folate levels below the genotype-specific thresholds was 1.6 (95% CI, 1.04–2.46). Similar results were obtained when RBC folate was considered as a measure of folate status (odds ratio = 1.8, 95% CI, 1.03–3.15). A gene-nutrient interaction that defines a higher risk for CAD is determined by folate levels below specific thresholds, which differ depending on the MTHFR 677 C->T genotype.

KEY WORDS: • MTHFR • folate • gene-nutrient interaction • coronary artery disease • homocysteine




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