This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hegele, R. A. Articles by Connelly, P. W. Search for Related Content PubMed PubMed Citation Articles by Hegele, R. A. Articles by Connelly, P. W. Related Collections Clinical genetics Lipids Risk Factors Genomics Genetics of cardiovascular disease

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:217.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

The Private Hepatocyte Nuclear Factor-1 G319S Variant Is Associated With Plasma Lipoprotein Variation in Canadian Oji-Cree

Robert A. Hegele; Henian Cao; Stewart B. Harris; Anthony J. G. Hanley; Bernard Zinman; Philip W. Connelly
Abstract—We previously showed an extremely strong association between type 2 diabetes and a private polymorphism, namely G319S, in the hepatocyte nuclear transcription factor (HNF)-1. Because HNF-1 is involved in the transcription of several apolipoprotein genes, we tested for an association between the private HNF1A G319S variant and plasma lipoproteins in a sample of 55 unrelated Oji-Cree subjects with type 2 diabetes and 175 unrelated Oji-Cree subjects without type 2 diabetes. In Oji-Cree subjects with type 2 diabetes, we found that the HNF1A G319S genotype was significantly associated with lower plasma concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein (apo) B. In Oji-Cree subjects without type 2 diabetes, we found that the HNF1A G319S genotype was significantly associated with higher plasma concentrations of high density lipoprotein cholesterol and apo AI. There were no associations with plasma triglycerides or lipoprotein(a). Regression analysis indicated that the HNF1A genotype accounted for 10% of the variation in the apo B–related traits in the diabetic subjects and for 5% of the variation in the apo AI–related traits in the nondiabetic subjects. Furthermore, the regression model indicated that the HNF1A S319 allele affected these traits in a dominant manner in subjects with and without type 2 diabetes. These findings provide the first evidence that a rare variant in a nuclear transcription factor is associated with variation in plasma lipoprotein traits.

Key Words: transcription factors • diabetes • polygenic traits • atherosclerosis

This article has been cited by other articles:

				L. E. Rufibach, S. A. Duncan, M. Battle, and S. S. Deeb Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter J. Lipid Res., July 1, 2006; 47(7): 1463 - 1477. [Abstract] [Full Text] [PDF]

				X. Wang and B. Paigen Genetics of Variation in HDL Cholesterol in Humans and Mice Circ. Res., January 7, 2005; 96(1): 27 - 42. [Abstract] [Full Text] [PDF]

				N. Babaya, H. Ikegami, T. Fujisawa, K. Nojima, M. Itoi-Babaya, K. Inoue, J. Nakura, M. Abe, M. Yamamoto, J. J. Jin, et al. Association of I27L Polymorphism of Hepatocyte Nuclear Factor-1{alpha} Gene with High-Density Lipoprotein Cholesterol Level J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2548 - 2551. [Abstract] [Full Text] [PDF]

				T. Langmann, M. Porsch-Ozcurumez, S. Heimerl, M. Probst, C. Moehle, M. Taher, H. Borsukova, D. Kielar, W. E. Kaminski, E. Dittrich-Wengenroth, et al. Identification of Sterol-independent Regulatory Elements in the Human ATP-binding Cassette Transporter A1 Promoter. ROLE OF Sp1/3, E-BOX BINDING FACTORS, AND AN ONCOSTATIN M-RESPONSIVE ELEMENT J. Biol. Chem., April 19, 2002; 277(17): 14443 - 14450. [Abstract] [Full Text] [PDF]