Predicting Hyperhomocysteinemia by Methylenetetrahydrofolate Reductase C677T Polymorphism in Chinese Patients With Hypertension.
OBJECTIVE
To evaluate the performance of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in predicting hyperhomocysteinemia (HHcy) in Chinese patients with hypertension.


METHODS
We measured plasma total homocysteine tHcy level and C677T genotype in 1058 Chinese patients with hypertension from 4 previous studies. We used 10, 15, and 20 μmol/L as cutoff values for the definition of mild, modest, and severe HHcy, respectively. Logistic models for HHcy were built from the study sample using the C677T genotype as well as age and gender as predictors. The receiver-operating characteristics of the models were evaluated.


RESULTS
Our major findings are that (1) C677T TT genotype is consistently associated with a higher tHcy across the 4 studies, with an increase in size ranging from 38% to 68% in the 4 studies and 51% overall. The C677T polymorphism independently explained about 14% of the total variance of the normalized tHcy. (2) The TT genotype is associated with a large increase in odds ratio (OR) for HHcy. Overall, the multivariate-adjusted ORs for the TT genotype are 3.9 (95% confidence interval [CI]: 2.4-6.4), 6.5 (95% CI: 4.0-10.6), and 17.9 (95% CI: 8.4-38.1) for mild, modest, and severe HHcy, respectively. (3) Overall, the predicting performance increased with HHcy severity, with sensitivity improving from 31.0% for mild HHcy to 70.3% for severe HHcy, and with specificity slightly decreasing from 85.4% to 80.3%. Inclusion of gender and age as predictors significantly improves the sensitivity, especially for predicting mild HHcy.


CONCLUSIONS
With an excellent sensitivity and a modest specificity, C677T could be a useful screening marker for severe HHcy.
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China.
Yu
Y
Wang
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China.
Xin
X
Xu
Department of Cardiology, Peking University First Hospital and Medical Department, Beijing, P. R. China.
Yong
Y
Huo
School of Life Sciences, Anhui University, Hefei, P. R. China Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei, P. R. China.
Dahai
D
Liu
Department of Pharmacy, Peking University First Hospital and Medical Department, Beijing, P. R. China.
Yimin
Y
Cui
Department of Clinical Pharmacology, Affiliated Hospital, Academic of Military Medical Sciences, Beijing, P. R. China.
Zeyuan
Z
Liu
Department of pharmacy, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, P. R. China.
Zhigang
Z
Zhao
Institute of Biomedicine, Anhui Medical University, Hefei, P. R. China.
Xiping
X
Xu
Beijing Fuwai Hospital, China Medical Academy, Beijing, P. R. China.
Lisheng
L
Liu
Department of Geriatric Cardiology, PLA General Hospital, Beijing, P. R. China.
Xiaoying
X
Li
School of Life Sciences, Anhui University, Hefei, P. R. China Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei, P. R. China Institute of Biomedicine, Anhui Medical University, Hefei, P. R. China shanqun@gmail.com.
Shanqun
S
Jiang
D000328:Adult; D000368:Aged; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000201:enzymology* / Q000235:genetics*; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
MTHFR; hyperhomocysteinemia; hypertension; polymorphism; prediction