Significance of a polymorphism (G-->A transition) in the -75 position of the apolipoprotein A-I gene promoter on serum high density lipoprotein-cholesterol levels in Japanese hyperlipidemic subjects.
High density lipoprotein-cholesterol (HDL-C) levels are inversely related to the incidence of coronary artery disease. We studied the influence of a G(-75)-->A transition in the promoter of the apolipoprotein (apo) A-I gene, a major protein component of HDL, on serum HDL-C levels in hyperlipidemic subjects. Seventy three hyperlipidemic subjects with serum levels of high HDL-C (HDL-C > or = 70 mg/dl, Group H) were compared with hyperlipidemic subjects with levels of HDL-C between 40 and 70 mg/dl (Group N) and those with HDL-C < 40 mg/dl (Group L). Group H showed a higher incidence (45.2%) of low plasma cholesteryl ester transfer protein (CETP) activity than Groups N (9.1%) and L (5.3%) (p < 0.001). Group H had a higher incidence of the G(-75)-->A transition (0.275) than Groups N (0.117, p < 0.05) and L (0.056, p < 0.01), among subjects with normal CETP activities. The HDL-C levels in subjects with the transition (84 +/- 16 mg/dl) were higher than those in subjects without the transition (56 +/- 12 mg/dl) (p < 0.05). These data suggest that a G(-75)-->A transition of the apo A-I gene promoter, in addition to the common mutation of CETP gene, contributes to high HDL-C levels among hyperlipidemic patients in Japan.
Tashiro
J
J
Department of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, Japan.
Morisaki
N
N
Kobayashi
J
J
Bujo
H
H
Kanzaki
T
T
Murano
S
S
Saito
Y
Y
D000225:Adenine / Q000737:chemistry*; D016632:Apolipoprotein A-I / Q000235:genetics*; D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D006023:Glycoproteins; D006147:Guanine / Q000737:chemistry*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D016632:Apolipoprotein A-I; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D006147:Guanine; D000225:Adenine