TY - JOUR
T1 - The effect of CYP7A1 polymorphisms on lipid responses to fenofibrate
AU - Shen, Jian
AU - Arnett, Donna K.
AU - Parnell, Laurence D.
AU - Lai, Chao Qiang
AU - Straka, Robert J.
AU - Hopkins, Paul N.
AU - An, Ping
AU - Feitosa, Mary F.
AU - Ordovás, José M.
PY - 2012/3
Y1 - 2012/3
N2 - INTRODUCTION: CYP7A1 encodes cholesterol 7α-hydroxylase, an enzyme crucial to cholesterol homeostasis. Its transcriptional activity is downregulated by fenofibrate. The goal of this study was to determine the effect of CYP7A1 polymorphisms on lipid changes in response to fenofibrate. METHODS: We examined the associations of 3 tagging single nuclear polymorphisms (i6782C>T, m204T>G, 3U12536A>C) at CYP7A1 with triglyceride (TG) and high-density lipoprotein cholesterol (HDL)-C responses to a 3-week treatment with 160 mg/d of fenofibrate in 864 US white participants from the Genetics of Lipid Lowering Drugs and Diet Network study. RESULTS: The m204T>G variant was significantly associated with TG and HDL-C responses with fenofibrate. Individuals homozygous for the common T allele of m204T>G single nuclear polymorphism displayed both the greater reduction of TG (-32% for TT,-28% for GT,-25% for GG, P = 0.004) and an increase of HDL-C response compared with noncarriers (4.1% for TT, 3.4% for GT, 1.2% for GG, P = 0.01). Conversely, individuals homozygous for the minor allele of i6782C>T showed a greater increase in the HDL-C response compared with noncarriers (2.8% CC, 4.5% for CT, 5.8% for TT, P = 0.02), albeit no significant effect on TG response. CONCLUSIONS: Our data suggest that common variants at the CYP7A1 locus modulate the TG-lowering and HDL-C-raising effects of fenofibrate, and contribute to the interindividual variation of the drug responses.
AB - INTRODUCTION: CYP7A1 encodes cholesterol 7α-hydroxylase, an enzyme crucial to cholesterol homeostasis. Its transcriptional activity is downregulated by fenofibrate. The goal of this study was to determine the effect of CYP7A1 polymorphisms on lipid changes in response to fenofibrate. METHODS: We examined the associations of 3 tagging single nuclear polymorphisms (i6782C>T, m204T>G, 3U12536A>C) at CYP7A1 with triglyceride (TG) and high-density lipoprotein cholesterol (HDL)-C responses to a 3-week treatment with 160 mg/d of fenofibrate in 864 US white participants from the Genetics of Lipid Lowering Drugs and Diet Network study. RESULTS: The m204T>G variant was significantly associated with TG and HDL-C responses with fenofibrate. Individuals homozygous for the common T allele of m204T>G single nuclear polymorphism displayed both the greater reduction of TG (-32% for TT,-28% for GT,-25% for GG, P = 0.004) and an increase of HDL-C response compared with noncarriers (4.1% for TT, 3.4% for GT, 1.2% for GG, P = 0.01). Conversely, individuals homozygous for the minor allele of i6782C>T showed a greater increase in the HDL-C response compared with noncarriers (2.8% CC, 4.5% for CT, 5.8% for TT, P = 0.02), albeit no significant effect on TG response. CONCLUSIONS: Our data suggest that common variants at the CYP7A1 locus modulate the TG-lowering and HDL-C-raising effects of fenofibrate, and contribute to the interindividual variation of the drug responses.
KW - CYP7A1
KW - TG response
KW - fenofibrate
KW - polymorphism
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U2 - 10.1097/FJC.0b013e31823de86b
DO - 10.1097/FJC.0b013e31823de86b
M3 - Article
C2 - 22075751
AN - SCOPUS:84858796882
SN - 0160-2446
VL - 59
SP - 254
EP - 259
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 3
ER -