TY - JOUR
T1 - A common haplotype on methylenetetrahydrofolate reductase gene modifies the effect of angiotensin-converting enzyme inhibitor on blood pressure in essential hypertension patients - A family-based association study
AU - Jiang, Shanqun
AU - Hsu, Yi Hsiang
AU - Niu, Tianhua
AU - Xu, Xin
AU - Xing, Houxun
AU - Chen, Changzhong
AU - Wang, Xiaobin
AU - Zhang, Yan
AU - Peng, Shaojie
AU - Xu, Xiping
N1 - Funding Information:
1School of Life Sciences, University of Science and Technology of China, Hefei, China 2Program for Population Genetics, Harvard School of Public Health, Boston, Massachusetts, USA 3Insitute of Biomedicine, Anhui Medical University, Hefei, China 4Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA 5Mary Ann and J. Milburn Smith Child Health Program, Children’s Memorial Hospital and Children’s Memorial Institute for Education and Research, Chicago, Illinois, USA
Funding Information:
This study was conducted by the Institute of Biomedicine, Anhui Medical University. We acknowledge the assistance from Aiqun Huang, Xiumei Hong, Yunxian Yu, and Shanchun Zhang of University of Science and Technology of China, and other researchers of Anhui Medical University and Harvard School of Public Health.
PY - 2005/8
Y1 - 2005/8
N2 - Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (ΔDBP and ΔSBP) to benazepril treatment (p = 0.003 and p = 0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of ΔDBP or ΔSBP. For residual of ΔDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of ΔSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.
AB - Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (ΔDBP and ΔSBP) to benazepril treatment (p = 0.003 and p = 0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of ΔDBP or ΔSBP. For residual of ΔDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of ΔSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.
KW - Angiotensin-converting enzyme inhibitor
KW - Essential hypertension
KW - Haplotype
KW - Methylenetetrahydrofolate reductase
KW - Pharmacogenetics
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U2 - 10.1081/CEH-200067686
DO - 10.1081/CEH-200067686
M3 - Article
C2 - 16081343
AN - SCOPUS:23844464118
SN - 1064-1963
VL - 27
SP - 509
EP - 521
JO - Clinical and Experimental Hypertension
JF - Clinical and Experimental Hypertension
IS - 6
ER -