Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity.

Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity. Research Abstract Details 

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Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity. Abstract Text:

Ping He,Michael H Court,David J Greenblatt,Lisa L von Moltke,

Human pregnane X receptor (hPXR) gene polymorphisms (spanning exon 2 to exon 5) and alternative mRNA splicing were investigated as possible contributors to individual variability in CYP3A metabolic activity measured both in vivo and in vitro. None of the 9 variants evaluated, including the 2 most common nonsynonymous variants (Pro27Ser and Gly36Arg), was found to be associated with midazolam 1'-hydroxylation rate measured in a bank of human livers (48 European Americans, 4 African Americans, 2 Hispanics). In contrast, 3 linked hPXR variants (g.252A > G, g.275A > G, and g.4760G > A) were significantly (P < .05) associated with oral midazolam clearance in a mixed race/ethnicity population (n = 26) and the African American subpopulation (n = 14) but not in European Americans (n = 9). Although the amount of hPXR mRNA normally spliced at the exon 4-5 junction correlated well with midazolam 1'-hydroxylation activities (P < .05), none of the 6 hPXR mRNA splice variants identified was associated with midazolam 1'-hydroxylation. In conclusion, several hPXR polymorphisms have been identified that may have predictive value for oral midazolam clearance, particularly in African Americans.

Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity. Publishing Authors By Initials

P He,MH Court,DJ Greenblatt,LL von Moltke,

For similar proteins: receptors, cytoplasmic and nuclear: receptors, steroid research abstracts see: proteins: receptors, cytoplasmic and nuclear: receptors, steroid research

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MEDLINE DATE:

Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of clinical pharmacology

VOLUME: 46

Page Numbers: 1356-69

Journal Abbreviation:

ISSN: 0091-2700

DAY: 3

MONTH: Nov

YEAR: 2006

Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 366372

Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity. Keywords Mesh Terms:

KEYWORDS: Receptors, Steroid

MESH TERMS: metabolism

Chemical & Substance for Abstract: Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity. Information

Substance Name: CYP3A protein, human

Registry Number: EC 1.14.14.1

Grant and Affiliation Information for Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity.

AFFILIATION: Division of Clinical Pharmacology, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.

Country: United States

AGENCY: United States NCRR

GRANT: RR-00054

ACRONYM: RR

MEDLINETA: J Clin Pharmacol

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