title: Insertion/deletion polymorphism in clusterin gene influences serum lipid levels and carotid intima-media thickness in hypertensive Japanese females.
abstract: Clusterin has been implicated in lipid metabolism and atherogenesis, however, the influence of genetic variation has not been examined in Japanese. In this study, we identified 11 single nucleotide polymorphisms (SNPs) of clusterin gene by direct sequencing. Among them, one promoter SNP (-4453T>G), one missense SNP (4183G>A), and 2 common SNPs (5608T>C and 6316delT) were genotyped in 525 asymptomatic hypertensives not treated with lipid lowering agents. -4453T>G, 4183G>A, and 5608T>C showed no correlation with the clinical characteristics, however, in the 6316delT, an insertion (I)/deletion (D) polymorphism, D/D subjects had significantly higher levels of total cholesterol and low-density lipoprotein (LDL)-cholesterol than I/I subjects in females but not in males. Female subjects with the D allele (D/D+I/D) had greater intima-media thickness of the carotid artery than I/I subjects. In a multiple logistic regression analysis, the D allele of 6316delT was detected as an independent predictor for the plaque prevalence. In conclusion, the clusterin gene polymorphism may contribute to the serum lipid levels and the progression of carotid atherosclerosis in hypertensive Japanese females.
authors.affiliation: Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Japan. ymiwa@clipharm.med.kyushu-u.ac.jp
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Miwa
authors.forename: Shin
authors.initials: S
authors.lastname: Takiuchi
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yoshii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Horio
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tanaka
authors.forename: Mariko
authors.initials: M
authors.lastname: Banno
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sasaguri
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kawano
mesh_terms: D000368:Aged; D001483:Base Sequence; D002339:Carotid Arteries / Q000473:pathology*; D051152:Clusterin; D017931:DNA Primers; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000473:pathology*; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D011110:Polymorphism, Genetic; D017539:Tunica Intima / Q000473:pathology*
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D017931:DNA Primers; D006023:Glycoproteins; D008055:Lipids; D018832:Molecular Chaperones