Association of I27L polymorphism of hepatocyte nuclear factor-1 alpha gene with high-density lipoprotein cholesterol level.
The serum level of high-density lipoprotein cholesterol (HDL-c), which protects against the development of atherosclerosis, is under genetic control. However, the genetic components responsible for the serum HDL-c level are yet to be determined. A recent knockout mouse study demonstrated that hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is an essential transcriptional regulator of HDL-c metabolism. In this study, the association of an HNF-1 alpha gene polymorphism, isoleucine (Ile) 27 leucine (Leu), with lipid parameters, in particular with serum HDL-c level, was studied in 356 unrelated Japanese men. Though no significant difference was observed in total cholesterol and triglyceride levels among the three genotypes, the serum HDL-c level was significantly associated with the genotype (P < 0.01, trend test). Subjects with the Ile/Ile genotype had low serum HDL-c levels, and those with the Leu/Leu genotype had high serum HDL-c levels. These results demonstrate that the HNF-1 alpha gene locus is associated with serum HDL-c level and suggest that the Ile27 allele is a risk marker for atherosclerosis.
Babaya
Naru
N
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Ikegami
Hiroshi
H
Fujisawa
Tomomi
T
Nojima
Koji
K
Itoi-Babaya
Michiko
M
Inoue
Kaori
K
Nakura
Jun
J
Abe
Michiko
M
Yamamoto
Miyuki
M
Jin
Jin Ji
JJ
Wu
Zhihong
Z
Miki
Tetsuro
T
Fukuda
Masakatsu
M
Ogihara
Toshio
T
D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood*; D004268:DNA-Binding Proteins; D005838:Genotype; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007532:Isoleucine; D007930:Leucine; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics*
D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D007532:Isoleucine; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D007930:Leucine