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Association of I27L Polymorphism of Hepatocyte Nuclear Factor-1 Gene with High-Density Lipoprotein Cholesterol Level

Department of Geriatric Medicine (N.B., H.I., T.F., K.N., M.I.-B., K.I., T.O.), Osaka University Graduate School of Medicine, Osaka 565-0871; Department of Geriatric Medicine (J.N., M.A., M.Y., J.J.J., Z.W., T.M.), Ehime University School of Medicine, Ehime 791-0295; and Department of Ophthalmology (M.F.), Nippon Telegraph and Telephon West Osaka Hospital, Osaka 543-0042, Japan

Address all correspondence and requests for reprints to: Hiroshi Ikegami, M.D., Ph.D., Department of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: ikegami{at}geriat.med.osaka-u.ac.jp.

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 (HNF-1) is an essential transcriptional regulator of HDL-c metabolism. In this study, the association of an HNF-1 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 gene locus is associated with serum HDL-c level and suggest that the Ile27 allele is a risk marker for atherosclerosis.

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan.

Abbreviations: apo A-I, Apolipoprotein A-I; BMI, body mass index; HDL, high-density lipoprotein; HDL-c, HDL cholesterol; HNF, hepatocyte nuclear factor; Ile, isoleucine; LDL, low-density lipoprotein; LDL-c, LDL cholesterol; Leu, leucine; MODY, maturity-onset diabetes of the young; SNP, single-nucleotide polymorphism; TCF1, transcription factor 1; T-chol, total cholesterol.

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