TY - JOUR
T1 - Insertion/deletion polymorphism in clusterin gene influences serum lipid levels and carotid intima-media thickness in hypertensive Japanese females
AU - Miwa, Yoshikazu
AU - Takiuchi, Shin
AU - Kamide, Kei
AU - Yoshii, Masayoshi
AU - Horio, Takeshi
AU - Tanaka, Chihiro
AU - Banno, Mariko
AU - Miyata, Toshiyuki
AU - Sasaguri, Toshiyuki
AU - Kawano, Yuhei
N1 - Funding Information:
We are grateful to Yoko Tokunaga and Chiyako Imai for their excellent technical assistance. This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety and Research of Japan.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/6/17
Y1 - 2005/6/17
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2005.04.069
DO - 10.1016/j.bbrc.2005.04.069
M3 - Article
C2 - 15883054
AN - SCOPUS:21044454051
SN - 0006-291X
VL - 331
SP - 1587
EP - 1593
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -