TY - JOUR
T1 - Interactions between the single nucleotide polymorphisms in the homocysteine pathway (MTHFR 677C > T, MTHFR 1298 A > C, and CBSins) and the efficacy of HMG-CoA reductase inhibitors in preventing cardiovascular disease in high-risk patients of hypertension: the GenHAT study
AU - Maitland-van der Zee, Anke-Hilse
AU - Lynch, Amy
AU - Boerwinkle, Eric
AU - Arnett, Donna K.
AU - Davis, Barry R.
AU - Leiendecker-Foster, Catherine
AU - Ford, Charles E.
AU - Eckfeldt, John H.
PY - 2008
Y1 - 2008
N2 - Background High homocysteine blood concentrations predispose to coronary artery disease and statins influence homocysteine levels. Aim To study whether genes that regulate homocysteine metabolism interact with statins to modify the risk of coronary heart disease (CHD) and other cardiovascular outcomes. Methods The Genetics of Hypertension Associated Treatment is an ancillary study of the Anti hypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The genotyped population in the Lipid-Lowering Trial of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial included 9624 participants randomly assigned to pravastatin or to usual care. The efficacy of pravastatin in reducing risk of all-cause mortality and CHD was compared among genotype strata (MTHFR 677 CC, CT, and TT, MTHFR 1298 AA, AC, and CC, CBSins DD and 1(+)) by examining an interaction term in a proportional hazards model. Results No evidence existed of a pharmacogenetic effect on statins with the MTHFR 1298 A > C genotype for CHD risk. However, in persons with the CC variant for the MTHFR 677 C > T genotype, a significantly protective effect against CHD (0.71 (95% Cl 0.58-0.87A was shown, although in the CT [1.25 (95% Cl 0.97-1.61)] and TT groups [0.80 (95% Cl 0.50-1.28)] there were no such effects (interaction hazard ratio P=0.004). The CBSins, 1+ variant was associated with a significantly reduced risk for CHD among those on statin treatment [0.58 (95% CI 0.44-0.78)] whereas the DD genotype showed no effect of statin therapy [1.01 (95% Cl 0.84-1.20; P=0.002 for interaction]. For the endpoint all-cause mortality, no significant differences in efficacy were noted. Conclusion Polymorphisms in genes in the homocysteine pathway (MTHFR 677 C > T and CBSins) appear to modify the efficacy of pravastatin in reducing risk of cardiovascular events
AB - Background High homocysteine blood concentrations predispose to coronary artery disease and statins influence homocysteine levels. Aim To study whether genes that regulate homocysteine metabolism interact with statins to modify the risk of coronary heart disease (CHD) and other cardiovascular outcomes. Methods The Genetics of Hypertension Associated Treatment is an ancillary study of the Anti hypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The genotyped population in the Lipid-Lowering Trial of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial included 9624 participants randomly assigned to pravastatin or to usual care. The efficacy of pravastatin in reducing risk of all-cause mortality and CHD was compared among genotype strata (MTHFR 677 CC, CT, and TT, MTHFR 1298 AA, AC, and CC, CBSins DD and 1(+)) by examining an interaction term in a proportional hazards model. Results No evidence existed of a pharmacogenetic effect on statins with the MTHFR 1298 A > C genotype for CHD risk. However, in persons with the CC variant for the MTHFR 677 C > T genotype, a significantly protective effect against CHD (0.71 (95% Cl 0.58-0.87A was shown, although in the CT [1.25 (95% Cl 0.97-1.61)] and TT groups [0.80 (95% Cl 0.50-1.28)] there were no such effects (interaction hazard ratio P=0.004). The CBSins, 1+ variant was associated with a significantly reduced risk for CHD among those on statin treatment [0.58 (95% CI 0.44-0.78)] whereas the DD genotype showed no effect of statin therapy [1.01 (95% Cl 0.84-1.20; P=0.002 for interaction]. For the endpoint all-cause mortality, no significant differences in efficacy were noted. Conclusion Polymorphisms in genes in the homocysteine pathway (MTHFR 677 C > T and CBSins) appear to modify the efficacy of pravastatin in reducing risk of cardiovascular events
U2 - https://doi.org/10.1097/FPC.0b013e3282fe1759
DO - https://doi.org/10.1097/FPC.0b013e3282fe1759
M3 - Article
C2 - 18622257
SN - 1744-6872
VL - 18
SP - 651
EP - 656
JO - Pharmacogenetics and genomics
JF - Pharmacogenetics and genomics
IS - 8
ER -