Yu Wang1, Xin Xu1, Yong Huo2, Dahai Liu3, Yimin Cui4, Zeyuan Liu5, Zhigang Zhao6, Xiping Xu7, Lisheng Liu8, Xiaoying Li9, Shanqun Jiang10. 1. Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China. 2. Department of Cardiology, Peking University First Hospital and Medical Department, Beijing, P. R. China. 3. 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. 4. Department of Pharmacy, Peking University First Hospital and Medical Department, Beijing, P. R. China. 5. Department of Clinical Pharmacology, Affiliated Hospital, Academic of Military Medical Sciences, Beijing, P. R. China. 6. Department of pharmacy, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, P. R. China. 7. Institute of Biomedicine, Anhui Medical University, Hefei, P. R. China. 8. Beijing Fuwai Hospital, China Medical Academy, Beijing, P. R. China. 9. Department of Geriatric Cardiology, PLA General Hospital, Beijing, P. R. China. 10. 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.
Abstract
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. CONCLUSION: With an excellent sensitivity and a modest specificity, C677T could be a useful screening marker for severe HHcy.
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 homocysteinetHcy 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. CONCLUSION: With an excellent sensitivity and a modest specificity, C677T could be a useful screening marker for severe HHcy.