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Nutrients 2015, 7(8), 6670-6687; doi:10.3390/nu7085303

Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency

Institute of Health Sciences, Anhui University, Hefei 230601, Anhui, China
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
KIZ-SU Joint Laboratory of Animal Models and Drug Development, College of Pharmaceutical Sciences, Soochow University, Kunming 650223, Yunnan, China
Collaborative Innovation Center for Natural Products and Biological Drugs of Yunnan, Kunming 650223, Yunnan, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 29 June 2015 / Revised: 29 July 2015 / Accepted: 4 August 2015 / Published: 10 August 2015
(This article belongs to the Special Issue Diet and Metabolic Dysfunction)
View Full-Text   |   Download PDF [180 KB, uploaded 10 August 2015]


Folate deficiency is strongly associated with cardiovascular disease. We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chinese hypertensive population. A total of 480 subjects aged 28–75 were enrolled in this study from September 2005–December 2005 from six hospitals in different Chinese regions. Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay. Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA p = 0.030, respectively). However, the MTHFR A1298C mutation may confer protection by elevating the serum folate level (p = 0.025). Furthermore, patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers, especially those carrying four risk genotypes. These findings were verified by generalized multifactor dimensionality reduction (p = 0.0107) and a cumulative effects model (p = 0.001). The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk. View Full-Text
Keywords: MTHFR C677T; MTHFR A1298C; MTR A2756G; MTRR A66G; folate deficiency MTHFR C677T; MTHFR A1298C; MTR A2756G; MTRR A66G; folate deficiency
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, W.-X.; Dai, S.-X.; Zheng, J.-J.; Liu, J.-Q.; Huang, J.-F. Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency. Nutrients 2015, 7, 6670-6687.

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