Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jun;2(3):244-54.
doi: 10.1161/CIRCGENETICS.108.839506. Epub 2009 Apr 6.

Common coding variants of the HNF1A gene are associated with multiple cardiovascular risk phenotypes in community-based samples of younger and older European-American adults: the Coronary Artery Risk Development in Young Adults Study and The Cardiovascular Health Study

Alexander P Reiner  1 , Myron D Gross, Christopher S Carlson, Suzette J Bielinski, Leslie A Lange, Myriam Fornage, Nancy S Jenny, Jeremy Walston, Russell P Tracy, O Dale Williams, David R Jacobs Jr, Deborah A Nickerson
Affiliations

Common coding variants of the HNF1A gene are associated with multiple cardiovascular risk phenotypes in community-based samples of younger and older European-American adults: the Coronary Artery Risk Development in Young Adults Study and The Cardiovascular Health Study

Alexander P Reiner et al. Circ Cardiovasc Genet. 2009 Jun.

Abstract

Background: The transcription factor hepatocyte nuclear factor (HNF)-1 alpha regulates the activity of a number of genes involved in innate immunity, blood coagulation, lipid and glucose transport and metabolism, and cellular detoxification. Common polymorphisms of the HNF-1 alpha gene (HNF1A) were recently associated with plasma C-reactive protein and gamma-glutamyl transferase concentration in middle-aged to older European Americans (EA).

Methods and results: We assessed whether common variants of HNF1A are associated with C-reactive protein, gamma-glutamyl transferase, and other atherosclerotic and metabolic risk factors, in the large, population-based Coronary Artery Risk Development in Young Adults Study of healthy young EA (n=2154) and African American (AA; n=2083) adults. The minor alleles of Ile27Leu (rs1169288) and Ser486Asn (rs2464196) were associated with 0.10 to 0.15 standard deviation units lower C-reactive protein and gamma-glutamyl transferase levels in EA. The same HNF1A coding variants were associated with higher low-density lipoprotein cholesterol, apolipoprotein B, creatinine, and fibrinogen in EA. We replicated the associations between HNF1A coding variants and C-reactive protein, fibrinogen, low-density lipoprotein cholesterol, and renal function in a second population-based sample of EA adults 65 years and older from the Cardiovascular Health Study. The HNF1A Ser486Asn and/or Ile27Leu variants were also associated with increased risk of subclinical coronary atherosclerosis in Coronary Artery Risk Development in Young Adults and with incident coronary heart disease in Cardiovascular Health Study. The Ile27Leu and Ser486Asn variants were 3-fold less common in AA than in EA. There was little evidence of association between HNF1A genotype and atherosclerosis-related phenotypes in AA.

Conclusions: Common polymorphisms of HNF1A seem to influence multiple phenotypes related to cardiovascular risk in the general population of younger and older EA adults.

PubMed Disclaimer

References

    1. Cereghini S. Liver-enriched transcription factors and hepatocyte differentiation. FASEB J. 1996;10:267–82. - PubMed
    1. Roeder RG. Role of general and gene-specific cofactors in the regulation of eukaryotic transcription. Cold Spring Harb Symp Quant Biol. 1998;63:201–18. - PubMed
    1. Pontoglio M. Hepatocyte nuclear factor 1, a transcription factor at the crossroads of glucose homeostasis. J Am Soc Nephrol. 2000;11(Suppl 16):S140–3. - PubMed
    1. Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, Volkert TL, Schreiber J, Rolfe PA, Gifford DK, Fraenkel E, Bell GI, Young RA. Control of pancreas and liver gene expression by HNF transcription factors. Science. 2004;303:1378–81. - PMC - PubMed
    1. Shih DQ, Stoffel M. Dissecting the transcriptional network of pancreatic islets during development and differentiation. Proc Natl Acad Sci U S A. 2001;98:14189–91. - PMC - PubMed

Publication types

MeSH terms

Grants and funding