A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population.
To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 ( ABCA1) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1. After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(-273)C ( P=0.0074), C(-297)T ( P=0.0195), and IMS-JST071749 ( P=0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(-273)C genotype was influential in another set of subjects ( P=0.0310, n=743). However, the distribution of the ABCA1 G(-273)C genotype in subjects with MI ( n=598) was not different from that in the control population ( n=801). These results indicate that ABCA1 G(-273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.
Shioji
Keisuke
K
Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Nishioka
Junko
J
Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Naraba
Hiroaki
H
Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Kokubo
Yoshihiro
Y
Department of Preventive Cardiology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Mannami
Toshifumi
T
Department of Preventive Cardiology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Inamoto
Nozomu
N
Department of Preventive Cardiology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Kamide
Kei
K
Division of Hypertension and Nephrology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Takiuchi
Shin
S
Division of Hypertension and Nephrology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Yoshii
Masayoshi
M
Division of Hypertension and Nephrology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Miwa
Yoshikazu
Y
Division of Hypertension and Nephrology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Kawano
Yuhei
Y
Division of Hypertension and Nephrology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Miyata
Toshiyuki
T
Department of Preventive Cardiology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Miyazaki
Shunichi
S
Division of Cardiology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Goto
Yoichi
Y
Division of Cardiology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Nonogi
Hiroshi
H
Division of Cardiology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Tago
Naomi
N
Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Iwai
Naoharu
N
Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. niwai@res.ncvc.go.jp.
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D008076:Cholesterol, HDL / Q000097:blood*; D004247:DNA / Q000737:chemistry; D005091:Exons; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D004247:DNA