Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: a cross-sectional study.
BACKGROUND
Dyslipidemia is a well-established risk factor for cardiovascular disease. Serum lipids were affected by several gene polymorphisms, folate, homocysteine and other metabolite levels. We aim to investigate the effects of homocysteine metabolism enzyme polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) and their interactions with folate, homocysteine on serum lipid levels in Chinese patients with hypertension.


METHODS
Participants were 480 hypertensive adults that enrolled in September to December 2005 from six different Chinese hospitals (Harbin, Shanghai, Shenyang, Beijing, Xi'an, and Nanjing). Known MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G genotypes were determined by PCR-RFLP methods. Serum folate was measured by chemiluminescent immunoassay, homocysteine was measured by high-performance liquid chromatography, serum lipids parameters were determined by an automatic biochemistry analyzer, low-density lipoprotein was calculated by Friedewald's equation. Unitary linear regression model was used to assess the associations of gene polymorphisms, folate and homocysteine on serum lipid profiles. Unconditional logistic regression model was applied to test the interactions of folate, homocysteine and gene polymorphisms on dyslipidemia.


RESULTS
No correlations between gene polymorphisms and homocysteine on serum lipid profiles. Compared with normal folate patients, patients with low folate showed higher odds of hypertriglyceridemia (OR = 2.02, 95 % CI: 1.25-3.25, P = 0.004) and low levels of high-density lipoprotein cholesterol (OR = 1.88, 95 % CI: 1.07-3.28, P = 0.027). Each of four gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) combined with low folate showed higher odds of hypertriglyceridemia (P for trend: 0.049, 0.004, 0.007 and 0.005, respectively). MTHFR C677T and A1298C with low folate showed higher odds of low levels of high-density lipoprotein cholesterol (P for trend: 0.008 and 0.031).


CONCLUSIONS
Low folate status and homocysteine metabolism gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) may have a synergistic effect increased the incidence of dyslipidemia in Chinese hypertensive population.
Institute of Health Sciences, Anhui University, Hefei, 230601, PR China. liwenxin@mail.kiz.ac.cn.|State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, PR China. liwenxin@mail.kiz.ac.cn.
Wen-Xing
WX
Li
School of Life Sciences, Anhui University, Hefei, 230601, PR China. lvww@ahu.edu.cn.
Wen-Wen
WW
Lv
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, PR China. daishaoxing@mail.kiz.ac.cn.
Shao-Xing
SX
Dai
School of Life Sciences, Anhui University, Hefei, 230601, PR China. mingluopan@163.com.
Ming-Luo
ML
Pan
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, PR China. huangjf@mail.kiz.ac.cn.|KIZ-SU Joint Laboratory of Animal Models and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, PR China. huangjf@mail.kiz.ac.cn.|Collaborative Innovation Center for Natural Products and Biological Drugs of Yunnan, Kunming, 650223, PR China. huangjf@mail.kiz.ac.cn.
Jing-Fei
JF
Huang
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000097:blood / Q000235:genetics*; D000368:Aged; D002681:China; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000097:blood / Q000235:genetics*; D005492:Folic Acid / Q000097:blood*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; 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