title: Genetic variants in PCSK9 affect the cholesterol level in Japanese.
abstract: Mutations in the proprotein convertase subtilisin/kexin 9 ( PCSK9) gene have been reported in affected members of two families with autosomal dominant hypercholesterolemia. To investigate the effects of common variants in PCSK9 on the cholesterol level, we conducted an association study using a large cohort representing the general population in Japan (n=1,793). Direct sequencing in all of the exonic regions identified 21 polymorphisms. After consideration of linkage disequilibrium among these polymorphisms, we selected and genotyped nine polymorphisms by the TaqMan method. The intron 1/C(-161)T and exon 9/I474 V polymorphisms were associated with levels of total cholesterol (TC) [C(-161)T, P=0.0285; I474 V, P=0.0069] and low-density lipoprotein cholesterol (LDL-C) [C(-161)T, P=0.0257; I474 V, P=0.0007]. The distributions of these polymorphisms in subjects with miocardial infarction (MI) (n=649) were not different from those in the control population. These results provide the first evidence that common variants intron 1/C(-161)T and exon 9/I474 V in PCSK9 significantly affect TC and LDL-C levels in the general population in Japan.
authors.affiliation: Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai Suita, Osaka 565-8565, Japan.|The Organization for Pharmaceutical Safety and Research of Japan, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shioji
authors.affiliation: Department of Preventive Cardiology, National Cardiovascular Center, Osaka, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Mannami
authors.affiliation: Department of Preventive Cardiology, National Cardiovascular Center, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kokubo
authors.affiliation: Department of Preventive Cardiology, National Cardiovascular Center, Osaka, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Inamoto
authors.affiliation: Division of Cardiology, National Cardiovascular Center, Osaka, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takagi
authors.affiliation: Division of Cardiology, National Cardiovascular Center, Osaka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Division of Cardiology, National Cardiovascular Center, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonogi
authors.affiliation: Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai Suita, Osaka 565-8565, Japan. niwai@res.ncvc.go.jp.
authors.forename: Naoharu
authors.initials: N
authors.lastname: Iwai
mesh_terms: D001483:Base Sequence; D002784:Cholesterol / Q000097:blood*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases