A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression.

A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression. Research Abstract Details 

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A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression. Abstract Text:

Catia Marzolini,Rommel G Tirona,Guillermo Gervasini,Balasubramanian Poonkuzhali,Mahfoud Assem,Wooin Lee,Brenda F Leake,John D Schuetz,Erin G Schuetz,Richard B Kim,

The farnesoid X receptor (FXR or NR1H4) is an important bile-acid-activated, transcriptional regulator of genes involved in bile acid, lipid, and glucose homeostasis. Accordingly, interindividual variations in FXR expression and function could manifest as variable susceptibility to conditions such as cholesterol gallstone disease, atherosclerosis, and diabetes. We performed an FXR polymorphism discovery analysis of European-, African-, Chinese-, and Hispanic-Americans and identified two rare gain-of-function variants and a common single nucleotide polymorphism resulting in a G-1T substitution in the nucleotide adjacent to the translation initiation site (FXR*1B) with population allelic frequencies ranging from 2.5 to 12%. In cell-based transactivation assays, FXR*1B (-1T) activity was reduced compared with FXR*1A (-1G). This reduced activity for FXR*1B resulted from neither decreased translational efficiency nor the potential formation of a truncated translational variant. To further define the relevance of this polymorphism, gene expression was examined in a human liver bank to reveal that levels of the FXR target genes small heterodimer partner and organic anion transporting polypeptide 1B3 were significantly reduced in livers harboring an FXR*1B allele. These findings are the first to identify the presence of a common genetic variant in FXR with functional consequences that could contribute to disease risk or therapeutic outcomes.

A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression. Publishing Authors By Initials

C Marzolini,RG Tirona,G Gervasini,B Poonkuzhali,M Assem,W Lee,BF Leake,JD Schuetz,EG Schuetz,RB Kim,

For similar proteins: transcription factors research abstracts see: proteins: transcription factors research

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A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular endocrinology (Baltimore, Md.)

VOLUME: 21

Page Numbers: 1769-80

Journal Abbreviation: Mol. Endocrinol.

ISSN: 0888-8809

DAY: 22

MONTH: 05

YEAR: 2007

A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression. Information

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LANGUAGE: eng

NlmUniqueID: 8801431

A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression. Keywords Mesh Terms:

KEYWORDS: Transcription Factors

MESH TERMS: physiology

Chemical & Substance for Abstract: A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression. Information

Substance Name: farnesoid X-activated receptor

Registry Number: 0

Grant and Affiliation Information for A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression.

AFFILIATION: Division of Clinical Pharmacology, Department of Medicine, The University of Western Ontario, London Health Sciences Centre, University Hospital, London, Ontario, Canada N6A 5A5.

Country: United States

AGENCY: United States NIGMS

GRANT: GM61393

ACRONYM: GM

MEDLINETA: Mol Endocrinol

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