Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency.
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.
Institute of Health Sciences, Anhui University, Hefei 230601, Anhui, China. liwenxin@mail.kiz.ac.cn.|State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China. liwenxin@mail.kiz.ac.cn.
Wen-Xing
WX
Li
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China. daishaoxing@mail.kiz.ac.cn.
Shao-Xing
SX
Dai
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China. zhengjunjuan@mail.kiz.ac.cn.
Jun-Juan
JJ
Zheng
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China. liujiaqian@mail.kiz.ac.cn.
Jia-Qian
JQ
Liu
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China. huangjf@mail.kiz.ac.cn.|KIZ-SU Joint Laboratory of Animal Models and Drug Development, College of Pharmaceutical Sciences, Soochow University, Kunming 650223, Yunnan, China. huangjf@mail.kiz.ac.cn.|Collaborative Innovation Center for Natural Products and Biological Drugs of Yunnan, Kunming 650223, Yunnan, China. huangjf@mail.kiz.ac.cn.
Jing-Fei
JF
Huang
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure; D015992:Body Mass Index; D004311:Double-Blind Method; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency / Q000097:blood / Q000235:genetics*; D060005:Genotyping Techniques; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
D006710:Homocysteine; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human
MTHFR A1298C; MTHFR C677T; MTR A2756G; MTRR A66G; folate deficiency